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 .
Formal Matters
Applicant’s claim amendments and arguments in the reply filed on 23 June 2026 are acknowledged and have been fully considered. Claims 1-3, 5-9, and 20-24 are pending. Claims 1-3, 5-9, and 21-24 are under consideration in the instant office action. Claim 20 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and/or species, there being no allowable generic or linking claims. Claims 4 and 10-19 are canceled. Applicant amended claims 1-3, 5-9, and 20. Claims 21-24 are newly added. Applicant’s claim amendments and arguments necessitated a new ground of rejections under 35 USC 103 as set forth below. Accordingly, this office action is made final.
Withdrawn Objections/Rejections
Rejections and/or objections not reiterated from the previous office actions are hereby withdrawn as are those rejections and/or objections expressly stated to be withdrawn.
Moot Arguments
Applicant’s arguments with respect to claim(s) 1-3, 5-9, and 21-24 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
New Rejections Necessitated by Amendments
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.
Claim 21 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 21 recites “The biodegradable implant of claim 1, wherein the biodegradable implant is free of internal interconnected pores.” The recitation “free of internal interconnected pores” lacks an objective metes-and-bounds standard.
The claim does not identify how “internal” is distinguished from the “surface” already recited in claim 1, what constitutes an “interconnected” pore (open-cell network versus closed voids, minimum connectivity, percolation path to the exterior, etc.), or the method and threshold used to determine that the implant is “free of”. One of ordinary skill in the art cannot determine, with reasonable certainty, when an implant that already has a surface “free of interconnected pores” does or does not meet claim 21. Additionally, the relationship to the “solid” and “surface … free of interconnected pores” limitations of claim 1 is unclear.
Claim 1 already requires a solid implant whose surface lacks interconnected pores. Claim 21 then requires the implant as a whole to be free of internal interconnected pores. It is unclear whether claim 21 (a) merely restates or slightly restates the solid/surface limitations already present in claim 1, (b) requires the entire bulk (core and any subsurface region) to contain no interconnected pore network, or (c) permits closed/isolated internal voids so long as they are not interconnected. The specification does not supply a definition or a working example that measures internal versus surface porosity with a stated method and cutoff. The resulting ambiguity renders the scope of claim 21 unascertainable. Furthermore, the phrase “free of internal interconnected pores” is a negative functional limitation. Without an accompanying measurement protocol or quantitative criterion in the claim or a clear definition in the specification that one of ordinary skill in the art would understand as limiting, the public is not reasonably informed of the boundary between infringing and non-infringing implants.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 21 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 21 depends from claim 1. Claim 1 already requires that the biodegradable implant is solid and that a surface of the biodegradable implant is free of interconnected pores. A solid implant whose exterior surface lacks interconnected pores is reasonably understood, in the context of melt-processed or in-situ-formed polyester implants, to be a dense matrix that does not present an open, percolating pore network from the interior to the surface. Claim 21’s additional recitation that the implant is “free of internal interconnected pores” does not add a further structural or compositional limitation that is independent of, or narrower than, the “solid” + “surface free of interconnected pores” combination already required by claim 1. If “internal interconnected pores” means an open pore network that communicates with the surface, that network is already excluded by claim 1’s surface limitation (an interconnected internal network that reaches the surface would make the surface not free of interconnected pores). If “internal” is intended to reach closed, non-percolating voids that never reach the surface, the claim still fails to identify a further limitation that one of ordinary skill in the art can apply, and the claim as written does not clearly add anything beyond the solid, surface-dense implant of claim 1.Because claim 21 does not further limit claim 1, it is improper under § 112(d). Applicants may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Note: The claims are examined with respect to the elected species wherein buprenorphine as the species of drug and the combination of poly(lactide-co-glycolide) and poly(ε-caprolactone) as the one or more biodegradable polymer.
Claims 1-3, 5-9, and 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Saxena et al. (WO 2022/175977, newly cited) in view of Norton et al. (US 2013/0210853, newly cited).
Applicants’ claims
Applicants claim 1 recites “A biodegradable implant comprising buprenorphine and one or more biodegradable polymers, wherein the biodegradable implant is solid; and wherein a surface of the biodegradable implant is free of interconnected pores.” Claim 2 recites “The biodegradable implant of claim 1, that comprises about 40 to 80% by weight of buprenorphine, based on the total weight of the biodegradable implant.” Claim 3 recites “The biodegradable implant of claim 1, that comprises about 50 to 70% by weight of buprenorphine, based on the total weight of the biodegradable implant.” Dependent claims thereof recite further limitations defining various features.
Claim Interpretation: “combination of PLGA and poly(ε-caprolactone)” encompasses physical blends of the two homopolymers/copolymers as well as lactide-glycolide-caprolactone terpolymers or PLGA + PCL-containing copolymers listed in Saxena et al.
“solid” is met by both pre-formed melt-extruded/compression-molded rods of Saxena et al. and in-situ-formed solid implants (Norton et al.).
“surface … free of interconnected pores” is reasonably interpreted as the absence of an open, percolating pore network at the exterior surface (functionally non-porous skin or dense melt-processed surface). The claim does not require a completely pore-free bulk or a specific porosity measurement method.
Determination of the Scope and Content of the Prior Art
(MPEP 2141.01)
Saxena et al. teach a biodegradable implant for the sustained release of buprenorphine, wherein the implant comprises: a) buprenorphine, or its salts, or prodrug thereof; in the concentration of about 9% w/w to 95% w/w of the total composition; b) a polymeric matrix comprising of biodegradable polymer, in a concentration of about 4%w/w to 90%w/w, having the particle diameter of between 10 pm to 150 pm; and c) a biodegradable lubricant in a concentration of about l% w/w to 15% w/w, wherein the buprenorphine in the biodegradable implant is continuously released over an extended period of time which is controlled by the rate of the polymer degradation and subsequent release of drug from the drug polymer matrix by diffusion, swelling or erosion that results in a consistent release of buprenorphine in the blood plasma for at least about one month to about one year (see claim 1). The biodegradable implant as claimed in claim la, comprises of buprenorphine preferably about 47.5% w/w of the total composition (see claim 2).The biodegradable implant as claimed in claim lb, wherein the biodegradable polymer is poly(lactic-co-glycolic acid) of variable compositions selected from the group consisting of (50/50), (75/25) and (85/15) grades preferably about 47.5% w/w of the total composition (see claim 3). The biodegradable implant as claimed in claim lc, wherein the biodegradable lubricant is glyceryl monostearate at about 5% w/w of the total composition (see claim 4). The biodegradable implant as claimed in claim 1, wherein the biodegradable implant comprises dimensions of about 1.0 to 8 mm in diameter and about 5 to 45 mm in length (see claim 5). The biodegradable implant as claimed in claim 5, wherein the biodegradable implant comprises dimensions of about 3 mm in diameter and about 45 mm in length (see claim 6). In one embodiment, the biodegradable polymer used in the present invention includes polyesters, poly(ether-esters), poly(ortho-esters), poly(amino acids), polyanhydrides, polyamides, polyphophazenes, polyphosphoesters, and copolymers therein known to ones skilled in the art. In certain embodiments disclosed herein are biodegradable polymers possessing degradation rates significantly slower than the release rate of therapeutic agent including but not limited to Polycaprolactone, Poly(L-lactide), Poly(DL-lactide), Poly(L-lactide-co- glycolide),Poly(lactic-co-glycolicacid), Poly(L-lactide-co-caprolactone), Poly(dioxanone) and Poly(glycolide-co-trimethylene carbonate). In preferred embodiments, the biodegradable polymer is Poly(lactic-co-glycolic acid) or PLGA (see page 6). To summarize Saxena et l. teach biodegradable buprenorphine implant (rod) for long-term delivery (about 6 months or more). Buprenorphine is embedded in a biodegradable polymer plus lubricant. Preferred polymer is PLGA; the specification expressly lists polycaprolactone, poly(L-lactide), poly(DL-lactide), poly(L-lactide-co-glycolide), PLGA, poly(L-lactide-co-caprolactone), poly(dioxanone), and poly(glycolide-co-trimethylene carbonate) as suitable polymers with slower degradation than the drug-release rate. Implants are made by hot-melt extrusion or compression/pressure molding into solid rods (typical diameter 1.5–5 mm, length 5–60 mm). Drug load examples 10–85% w/w buprenorphine with PLGA 4–95% w/w (see abstract; paragraphs describing polymer list; preferred PLGA embodiments; example 1 and process description (mixing, melting 100–150 °C, extrusion or molding into rods); claims 1–3 and process claims). Regarding the limitation of claim 21 Saxena et al, teach hot melt extrusion or compression molding of a buprenorphine/polyester blend with no porogen. That process inherently yields a dense solid rod whose interior does not contain an interconnected pore network.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP 2141.02)
Saxena et al. teach a solid biodegradable implant comprising buprenorphine and a biodegradable polymer, prepared by hot-melt extrusion or compression molding as described in detail above. The polymer of choice in Saxena et al. is PLGA; Saxena et al. also teach polycaprolactone and poly(L-lactide-co-caprolactone) as alternative or additional biodegradable polymers suitable for the same implant. However, Saxena et al. do not teach explicit working example that simultaneously uses both PLGA and PCL in the same matrix. Saxena et al. is silent with regard to the biodegradable implant being free of interconnected pores. These deficiencies are cured by the teachings of Norton et al.
Norton et al. teach solid biodegradable implants of buprenorphine formed from “combinations” of polylactide, polyglycolide, and polycaprolactone (i.e., PLGA + PCL or equivalent polyester combinations). It further teaches that the resulting solid implant may possess a skin that is functionally non-porous relative to any internal porosity. Norton et al. teach an injectable flowable composition comprising: at least one biodegradable thermoplastic polymer that is at least substantially insoluble in body fluid; a biocompatible polar aprotic organic liquid selected from the group consisting of one or more of an amide, an ester, a carbonate, a lactam, an ether, and a sulfonyl, wherein the biocompatible polar aprotic organic liquid has a solubility in aqueous medium or body fluid ranging from insoluble to completely soluble in all proportions; and, 1 wt % to 30 wt % of buprenorphine, a metabolite, or a prodrug thereof; wherein the composition is transformed in situ into a solid implant by contact with water, body fluid or other aqueous medium (see claim 1). The flowable composition of claim 1, wherein the biodegradable thermoplastic polymer is a polyester of one or more hydroxycarboxylic acids, or is a polyester of a combination of one or more diols and one or more dicarboxylic acids (see claim 2). The flowable composition of claim 2, wherein the polyester is selected from the group consisting of a polylactide, a polyglycolide, a polycaprolactone, a polyorthoester, a copolymer thereof, a terpolymer thereof, and combinations thereof (see claim 3). The solid implant has a solid matrix or a solid microporous matrix. The matrix can be a core surrounded by a skin. The implant may be solid and microporous. When microporous, the core preferably contains pores of diameters from about 1 to about 1000 microns. When microporous, the skin preferably contains pores of smaller diameters than those of the core pores. In addition, the skin pores are preferably of a size such that the skin is functionally non-porous in comparison with the core. The solid implant can optionally include, for example, one or more biocompatible organic substances which may function as an excipient as described above, or which may function as a plasticizer, a sustained release profile modifier, emulsifier, and/or isolation carrier for buprenorphine, a metabolite, or a prodrug thereof. The biocompatible organic liquid may also serve as an organic substance of the implant and/or may provide an additional function such as a plasticizer, a modifier, an emulsifier, or an isolation carrier. There may be two or more organic liquids present in the flowable composition such that the primary organic liquid acts as a mixing, solubilizing, or dispersing agent, and the supplemental organic liquid or liquids provide additional functions within the flowable composition and the implant. Alternatively, there may be one organic liquid which at least may act as a mixing, solubilizing, or dispersing agent for the other components, and may provide additional functions as well. As second or additional components, additional kinds of biodegradable organic liquids typically are combined with the flowable composition and may remain with the implant as the administered flowable composition coagulates (see paragraph 0028). The solid implant may also include, for example, a core that contains pores of diameters from about 1 to about 1000 microns, and optionally the skin contains pores of smaller diameters than those of the core pores, and optionally the skin pores are of a size such that the skin is functionally non-porous in comparison with the core (paragraph 0033). The thermoplastic polymer matrix is preferably a solid matrix and especially preferably is microporous. In an embodiment of the microporous solid matrix, there is a core surrounded by a skin. The core preferably contains pores of diameters from about 1 to about 1000 microns. The skin preferably contains pores of smaller diameters than those of the core pores. In addition, the skin pores are preferably of a size such that the skin is functionally non-porous in comparison with the core (paragraph 0121).
Finding of Prima Facie Obviousness Rational and Motivation
(MPEP 2142-2143)
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the instant invention to modify the teachings of by utilizing poly(ε-caprolactone) and PLGA combination or blend having a surface free of interconnected pores because Norton et al. teach solid biodegradable implants of buprenorphine formed from “combinations” of polylactide, polyglycolide, and polycaprolactone (i.e., PLGA + PCL or equivalent polyester combinations). It further teaches that the resulting solid implant may possess a skin that is functionally non-porous relative to any internal porosity. Norton et al. teach an injectable flowable composition comprising: at least one biodegradable thermoplastic polymer that is at least substantially insoluble in body fluid; a biocompatible polar aprotic organic liquid selected from the group consisting of one or more of an amide, an ester, a carbonate, a lactam, an ether, and a sulfonyl, wherein the biocompatible polar aprotic organic liquid has a solubility in aqueous medium or body fluid ranging from insoluble to completely soluble in all proportions; and, 1 wt % to 30 wt % of buprenorphine, a metabolite, or a prodrug thereof; wherein the composition is transformed in situ into a solid implant by contact with water, body fluid or other aqueous medium (see claim 1). The flowable composition of claim 1, wherein the biodegradable thermoplastic polymer is a polyester of one or more hydroxycarboxylic acids, or is a polyester of a combination of one or more diols and one or more dicarboxylic acids (see claim 2). The flowable composition of claim 2, wherein the polyester is selected from the group consisting of a polylactide, a polyglycolide, a polycaprolactone, a polyorthoester, a copolymer thereof, a terpolymer thereof, and combinations thereof (see claim 3). The solid implant has a solid matrix or a solid microporous matrix. The matrix can be a core surrounded by a skin. The implant may be solid and microporous. When microporous, the core preferably contains pores of diameters from about 1 to about 1000 microns. When microporous, the skin preferably contains pores of smaller diameters than those of the core pores. In addition, the skin pores are preferably of a size such that the skin is functionally non-porous in comparison with the core. The solid implant can optionally include, for example, one or more biocompatible organic substances which may function as an excipient as described above, or which may function as a plasticizer, a sustained release profile modifier, emulsifier, and/or isolation carrier for buprenorphine, a metabolite, or a prodrug thereof. The biocompatible organic liquid may also serve as an organic substance of the implant and/or may provide an additional function such as a plasticizer, a modifier, an emulsifier, or an isolation carrier. There may be two or more organic liquids present in the flowable composition such that the primary organic liquid acts as a mixing, solubilizing, or dispersing agent, and the supplemental organic liquid or liquids provide additional functions within the flowable composition and the implant. Alternatively, there may be one organic liquid which at least may act as a mixing, solubilizing, or dispersing agent for the other components, and may provide additional functions as well. As second or additional components, additional kinds of biodegradable organic liquids typically are combined with the flowable composition and may remain with the implant as the administered flowable composition coagulates (see paragraph 0028). The solid implant may also include, for example, a core that contains pores of diameters from about 1 to about 1000 microns, and optionally the skin contains pores of smaller diameters than those of the core pores, and optionally the skin pores are of a size such that the skin is functionally non-porous in comparison with the core (paragraph 0033). The thermoplastic polymer matrix is preferably a solid matrix and especially preferably is microporous. In an embodiment of the microporous solid matrix, there is a core surrounded by a skin. The core preferably contains pores of diameters from about 1 to about 1000 microns. The skin preferably contains pores of smaller diameters than those of the core pores. In addition, the skin pores are preferably of a size such that the skin is functionally non-porous in comparison with the core (paragraph 0121). One of ordinary skill in the art seeking to extend release duration or reduce initial burst (the explicit goals of both references) would have been motivated to blend the faster-degrading PLGA of Saxena et al. with slower-degrading PCL (already listed in Saxena et al. and expressly combinable in Norton et al.) to tune erosion rate and hydrophobicity. Doing so with the same melt-processing methods already used in Saxena et al. would inherently produce a dense solid rod whose exterior surface lacks interconnected pores—the same morphology Norton et al. family teach as a functionally non-porous skin. Saxena et al. in view of hot-melt extruding PLGA/PCL blends for solid implants as taught by Saxen et al. and Norton et al. who teach a functionally non-porous implant surface. Melt extrusion without porogen or residual solvent is known to yield a dense exterior; the claim limitation “surface … free of interconnected pores” is therefore the expected result of following the process already taught in Saxena et al. once PCL is added to the PLGA matrix. 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) (Claims to a printing ink comprising a solvent having the vapor pressure characteristics of butyl carbitol so that the ink would not dry at room temperature but would dry quickly upon heating were held invalid over a reference teaching a printing ink made with a different solvent that was nonvolatile at room temperature but highly volatile when heated in view of an article which taught the desired boiling point and vapor pressure characteristics of a solvent for printing inks and a catalog teaching the boiling point and vapor pressure characteristics of butyl carbitol.). Furthermore, in the case where any measurable parameters such as concentrations and amounts of drug and other ingredients" 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); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). Furthermore, differences in concentration or measurable parameters will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[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). One of ordinary skill in the art would have had a reasonable chance of success in combining the teachings of Saxena et al. and Norton et al. because both references are drawn to solid implants containing buprenorphine and biodegradable polymers for a sustained release of buprenorphine.
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. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim(s) 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Saxena et al. (WO 2022/175977, newly cited) in view of Norton et al. (US 2013/0210853, newly cited) as applied to claims 1-3, 5-9, and 21-23 above, and further in view of Norton et al. (US 2013/0202658, newly cited).
Applicants’ claims
Applicants claim 1 recites “A biodegradable implant comprising buprenorphine and one or more biodegradable polymers, wherein the biodegradable implant is solid; and wherein a surface of the biodegradable implant is free of interconnected pores. Claim 24 recites “The biodegradable implant of claim 1, wherein the biodegradable implant comprises particles of buprenorphine having a size distribution of less than about 150 µm.”
Determination of the Scope and Content of the Prior Art
(MPEP 2141.01)
The teachings of Saxena et al. and Norton et al. are described in detail above and are incorporated herein by reference.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP 2141.02)
Saxena et al. and Norton et al. do not explicitly teach wherein the biodegradable implant comprises particles of buprenorphine having a size distribution of less than about 150 µm. This deficiency is cured by the teachings of Norton et al. (US 2013/0202658).
Norton et al. (US 2013/0202658) a buprenorphine sustained release delivery system for treatment of conditions ameliorated by buprenorphine compounds. The sustained release delivery system includes a flowable composition containing a suspension of buprenorphine, a metabolite, or a prodrug thereof (see abstract). Preferably, the average particle size of the buprenorphine in the composition as hereinbefore described is less than 150μ, preferably less than 120μ, preferably less than 100μ, preferably less than 80μ, preferably less than 60μ, preferably less than 50μ, preferably less than 40μ. Especially preferably, the average particle size of the buprenorphine in the composition as hereinbefore described is less than 20μ, more especially preferably less than 10μ (see paragraphs 0014-0015).
Finding of Prima Facie Obviousness Rational and Motivation
(MPEP 2142-2143)
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the instant invention to modify the teachings of Saxena et al. and Norton et al. by including in the biodegradable implant particles of buprenorphine having a size distribution of less than about 150 µm because Norton et al. (US 2013/0202658) a buprenorphine sustained release delivery system for treatment of conditions ameliorated by buprenorphine compounds. The sustained release delivery system includes a flowable composition containing a suspension of buprenorphine, a metabolite, or a prodrug thereof (see abstract). Preferably, the average particle size of the buprenorphine in the composition as hereinbefore described is less than 150μ, preferably less than 120μ, preferably less than 100μ, preferably less than 80μ, preferably less than 60μ, preferably less than 50μ, preferably less than 40μ. Especially preferably, the average particle size of the buprenorphine in the composition as hereinbefore described is less than 20μ, more especially preferably less than 10μ (see paragraphs 0014-0015). One of ordinary skill in the art preparing the Saxena et al. or Norton et al. blend for hot melt extrusion or compression molding would have had every reason to reduce the buprenorphine to a size comparable to (or smaller than) the 10-150 μ polymer particles already specified. Doing so prevents segregation of a high load (up to 85% w/w) blend, improves content uniformity and melt homogeneity, and is the same particle-size range already used for buprenorphine in other parenteral long-acting products (Norton et al. (US 2013/0202658)) less than 150μ with working examples far smaller. No unexpected result is associated with the 150 μ cutoff; it is a conventional sieve size (100 mesh) used to remove oversize particles before melt processing. Combining the implant of Saxena et al. with the well-known buprenorphine particle size range of Norton et al. (US 2013/0202658), therefore renders claim 24 obvious. The combination teachings already used for claim 1 remains applicable; the particle size distribution limitation is an additional obvious process/starting material choice, not a patentable distinction. The examiner noted that size distribution of less than 150 μ is reasonably read as D90 or essentially all particles passing a 150 μ sieve (the usual meaning in pharmaceutical powder processing). Even a stricter “all particles less than 150 μ reading is met by the micronized examples of Norton et al. (US 2013/0202658) and by routine milling +100 mesh sieving. 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) (Claims to a printing ink comprising a solvent having the vapor pressure characteristics of butyl carbitol so that the ink would not dry at room temperature but would dry quickly upon heating were held invalid over a reference teaching a printing ink made with a different solvent that was nonvolatile at room temperature but highly volatile when heated in view of an article which taught the desired boiling point and vapor pressure characteristics of a solvent for printing inks and a catalog teaching the boiling point and vapor pressure characteristics of butyl carbitol.). Furthermore, in the case where any measurable parameters such as concentrations and amounts of drug and other ingredients and particle size distributions" 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); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). Furthermore, differences in concentration or measurable parameters such as particle size distribution will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[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). One of ordinary skill in the art would have had a reasonable chance of success in combining the teachings of Saxena et al., Norton et al., and Norton et al. (US 2013/0202658) because all of the references are drawn to compositions containing buprenorphine and biodegradable polymers for a sustained release of buprenorphine.
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. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 5-6, 8-9, and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-6, 8, and 11 of copending Application No. 19/250,827 (herein after ‘827) in view of Saxena et al. (WO 2022/175977, newly cited) in and Norton et al. (US 2013/0210853, newly cited).
Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-6, 8, and 11 of ‘827 in combination with Saxena et al. and Norton et al. render obvious instant claims of 1-3, 5-6, 8-9, and 21 of the instant application as explained below.
Claim 1 recites “A biodegradable implant comprising buprenorphine and one or more biodegradable polymers, wherein the biodegradable implant is solid; and wherein a surface of the biodegradable implant is free of interconnected pores.”
Corresponding claim 1 of ‘827 recites “A compacted biodegradable formulation comprising: a drug and one or more biodegradable polymers, wherein the formulation is essentially free of interconnected pores, and wherein the drug is a small molecule, a peptide, a protein, or a nucleic acid.” and claim 3 of ‘827 recites “The biodegradable formulation of claim 2, wherein the drug is a small molecule.” Claim 11 of ‘827 recites “The biodegradable formulation of claim 10, wherein the formulation is injectable.” These are species of the generic claim recited in claim 1 of the instant application.
Claim 2 recites “The biodegradable implant of claim 1, that comprises about 40 to 80% by weight of drug.”
Corresponding claim 2 of ‘827 recites “The biodegradable formulation of claim 1, comprising about 40% to about 80% by weight of the drug.”
Claim 5 recites “The biodegradable formulation of claim 4, wherein the buprenorphine is of the free base form, salt form, or mixtures thereof.”
Corresponding claim 4 of ‘827 recites “The biodegradable formulation of claim 3, wherein the drug is buprenorphine, a free base form thereof, a salt form thereof, or mixtures thereof.”
Claim 6 recites “The biodegradable formulation of claim 1, that comprises about 20 to 60% by weight of biodegradable polymer.”
Corresponding claim 5 of ‘827 recites “The biodegradable formulation of claim 2, wherein the formulation comprises about 20% to about 60% by weight of the biodegradable polymer.”
Claim 8 recites “The biodegradable formulation of claim 1, wherein the biodegradable polymer is at least one selected from the group consisting of poly(lactide-co-glycolide), poly(D,L-lactide), poly(ε-caprolactone), polyhydroxybutyrate, a polyanhydride, a polyorthoester, and any combination thereof.”
Corresponding claim 6 of ‘827 recites “The biodegradable formulation of claim 5, wherein the biodegradable polymer is poly(lactide-co-glycolide), poly(D,L-lactide), poly(ε-caprolactone), polyhydroxybutyrate, polyanhydrides, polyorthoesters, or combinations of any of these.”
Claim 9 recites “The biodegradable implant of claim 1, that provides sustained release of drug for about 90 days or longer.”
Corresponding claim 8 of ‘827 recites “The biodegradable formulation of claim 1, wherein the formulation provides sustained release of the drug for about 90 days or longer.”
Claim 21 recites “The biodegradable implant of claim 1, wherein the biodegradable implant is free of internal interconnected pores.”
‘827 differs from instant claims 1-3, 5-6, and 8-9 that ‘827 does not teach implant and in instant claim 1 it is the surface of the biodegradable implant which is free of interconnected pores. These deficiencies are cured by the teachings of Saxena et al. and Norton et al.
Saxena et al. teach a biodegradable implant for the sustained release of buprenorphine, wherein the implant comprises: a) buprenorphine, or its salts, or prodrug thereof; in the concentration of about 9% w/w to 95% w/w of the total composition; b) a polymeric matrix comprising of biodegradable polymer, in a concentration of about 4%w/w to 90%w/w, having the particle diameter of between 10 pm to 150 pm; and c) a biodegradable lubricant in a concentration of about l% w/w to 15% w/w, wherein the buprenorphine in the biodegradable implant is continuously released over an extended period of time which is controlled by the rate of the polymer degradation and subsequent release of drug from the drug polymer matrix by diffusion, swelling or erosion that results in a consistent release of buprenorphine in the blood plasma for at least about one month to about one year (see claim 1). Regarding the limitation of claim 21 Saxena et al, teach hot melt extrusion or compression molding of a buprenorphine/polyester blend with no porogen. That process inherently yields a dense solid rod whose interior does not contain an interconnected pore network.
Norton et al. teach solid biodegradable implants of buprenorphine formed from “combinations” of polylactide, polyglycolide, and polycaprolactone (i.e., PLGA + PCL or equivalent polyester combinations). It further teaches that the resulting solid implant may possess a skin that is functionally non-porous relative to any internal porosity.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the instant invention to modify the teachings of ‘827 by using its biodegradable formulation for forming an implant because Saxena et al. clearly teach the advantageous properties of using such a formulation in forming implants that can deliver the same active in sustained release manner. It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the instant invention to modify the teachings of ‘827 and Saxena et al. by making the surface free of interconnected pores because Norton et al. teach solid biodegradable implants of buprenorphine formed from “combinations” of polylactide, polyglycolide, and polycaprolactone (i.e., PLGA + PCL or equivalent polyester combinations). It further teaches that the resulting solid implant may possess a skin that is functionally non-porous relative to any internal porosity. One of ordinary skill in the art would avoid interconnected pores on the surface to prevent burst release of active. Doing so with the same melt-processing methods already used in Saxena et al. would inherently produce a dense solid rod whose exterior surface lacks interconnected pores—the same morphology Norton et al. teach as a functionally non-porous skin. Saxena et al. in view of hot-melt extruding PLGA/PCL blends for solid implants as taught by Saxen et al. and Norton et al. who teach a functionally non-porous implant surface. Melt extrusion without porogen or residual solvent is known to yield a dense exterior; the claim limitation “surface … free of interconnected pores” of ‘free of interconnected pores” is therefore the expected result of following the process already taught in Saxena et al. once PCL is added to the PLGA matrix as suggested by Norton et al.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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.
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/TIGABU KASSA/Primary Examiner, Art Unit 1619
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