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 .
Election/Restrictions
Applicant's election with traverse of Group I, drawn to an injectable composition, in the reply filed on 04/23/2026 is acknowledged. The traversal is on the grounds that the claims of Groups I-III share the same special technical feature and fall within permissible combinations under 37 C.F.R. § 1.475(b) of (2) A product and a process of use of said product and (4) A process and an apparatus or means specifically designed for carrying out the said process.
This is not found persuasive because, as set forth in the restriction requirement mailed 02/25/2026, while the groups share a technical feature, it does not rise to the level of a special technical feature that makes a contribution over the prior art, in view of the prior art of Sawhney (US 2010/0209478 A1, published August 19, 2010; included on IDS submitted 05/08/2024). In brief summary Sawhney teaches drug delivery using a dehydrated hydrogel with a therapeutic agent dispersed in the hydrogel (abstract); a syringe may be used to inject a hydrogel and/or microspheres and/or hydrogel precursors to form a depot (paragraph [0062]). The hydrogel or precursor can be used to deliver non-steroidal anti-inflammatory drugs (paragraphs [0149]-[0150]; Table 2), and microparticles formed from, e.g., PLGA can be used for drug delivery (paragraphs [0129]-[0130], [0150]). Sawhney teaches that therapeutic agents can be mixed with solvents (paragraph [0164]). Sawhney suggests drug release over the course of several days (paragraph [0227], point 6; Figures 10-11 and 14-17).
The requirement is still deemed proper and is therefore made FINAL.
Applicant's election with traverse of the species of NSAID of meloxicam in the reply filed on 02/25/2026 is acknowledged. The traversal is on the grounds that the NSAID species are described in the specification as members of a single genus useful in the same claimed composition architecture, and on the present record, no showing has been made that they are mutually exclusive or patentably distinct from one another.
This is not found persuasive because, as evidenced by the instant specification, NSAIDs are classified by chemical structure (with five distinct chemical structure classes) and mechanism of action (selective COX-1 inhibitor, selective COX-2 inhibitor, and mixed inhibitors) (paragraphs [0029]-[0031]). Thus, the evidence of record suggests that the species have distinct structures and mechanisms of action, and are not obvious variants of each other.
The requirement is still deemed proper and is therefore made FINAL.
Claims 42-46 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction requirement in the reply filed on 04/23/2026.
Claim 40 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the election requirement in the reply filed on 04/23/2026.
Claims 1-27 and 34-35 are cancelled.
Claims 28-33, 36-39, 41, and 47 are under current examination.
Priority
This application is a national stage entry of PCT/US2022/051358, filed 11/30/2022. Priority has been claimed to US PRO 63/285,169, filed 12/02/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/08/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements has been considered by the Examiner.
Claim Objections
Claims 28 and 47 are objected to because of the following informalities: it is believed that “a biodegradable polymer comprises poly(lactic-co-glycolic acid) (PLGA)” in lines 3, respectively, should read “a biodegradable polymer comprising poly(lactic-co-glycolic acid) (PLGA)”.
Claim 36 is objected to because of the following informalities: it is suggested that the comma between “dimethyl sulfoxide (DMSO)” and “or N-methyl-pyrrolidone (NMP)” should be omitted.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claim 47 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 47 recites “10-20% of a nonsteroidal anti-inflammatory drug” and “30-40% of a biodegradable polymer”. No units are associated with the recited percentages (i.e., % weight, % volume, etc.), which renders the metes and bounds of the claim uncertain. For purposes of examination and applying prior art, it is interpreted that these percentages are % weight.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 28-31, 36-37, and 41 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ibrahim et al. (“Development of meloxicam in situ implant formulation by quality by design principle” Drug Dev Ind Pharm, Early Online 2013, 1-8), hereafter “Ibrahim”.
Regarding instant claim 28, Ibrahim discloses an in situ implant formulation of meloxicam, a potent non-steroidal anti-inflammatory drug, with polylactide-co-glycolide (PLGA) and N-methyl pyrrolidone solvent (see entire document, particularly, Abstract, “Introduction” paragraph 1, and “Preparation of in situ implant formulations” at pg. 2). The formulations are administered via intramuscular injection (“Pharmokinetic Study” at pg. 3), and thus meet the limitation of being an injectable composition.
The limitation of instant claim 28, “wherein the injectable composition will form a solid biodegradable drug depot following a parenteral administration of the injectable composition to a subject in need and the solid biodegradable drug depot provides for the prolonged release of the NSAID for at least one day after administration of the injectable composition” is directed to a future intended use of the composition and properties which occur upon carrying out the intended use. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. As set forth above, Ibrahim discloses compositions which anticipate the structural components of the instant claim. Per MPEP 2112.01 I., “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).”, and further per MPEP 2112.01 II., "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”.
Nevertheless, Ibrahim further discloses that PLGA is biodegradable polymer (“Introduction” paragraph 2), that the formulations form an in situ implant which turns into a solid mass after contact with aqueous media (“Dissolution study” at pg. 2), that the formulations were injected intramuscularly (“Pharmokinetic Study” at pg. 3), and that the implant takes the form of a solidified gel (“Multivariate analysis” at pg. 3). As defined in the instant specification (paragraph [0065]), parenteral administration is inclusive of intramuscular injection. Ibrahim discloses meloxicam release over several days (see Figure 1 at pg. 4) and that the in situ implant formulation maintained the therapeutic level needed for COX-2 inhibition for 23 days (“Conclusion”). Thus, the formulations of Ibrahim will form a solid biodegradable drug depot which provides for the release of meloxicam for at least one day following parenteral administration.
Regarding instant claim 29, Ibrahim exemplifies formulations comprising 30% and 35% PLGA (Table 1 at pg. 3).
Regarding instant claim 30, the formulations of Ibrahim have a drug concentration of 10% w/w (“Preparation of in situ implant formulations” at pg. 2).
Regarding instant claim 31, the PLGA of Ibrahim is PLGA 50/50 (see “Materials” at pg. 2), and therefore meets the limitation of comprising at least 50% lactic acid units.
Regarding instant claims 36-37, the formulations of Ibrahim include N-methyl-pyrrolidone solvent (“Abstract” and “Preparation of in situ implant formulations” at pg. 2).
Regarding instant claim 41, as set forth above, the formulations of Ibrahim include the non-steroidal anti-inflammatory drug of meloxicam (see entire document, particularly Abstract and “Introduction” paragraph 1).
Claims 28, 33, 38, and 41 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wahab et al. (“Meloxicam Depot Parenteral Bio-Degradable Microspheres: Preparation, Characterization and In-Vivo Evaluation” Int. J. Pharm. Sci. Rev. Res. 2013, 21(2), 38-45), hereafter “Wahab”.
Regarding instant claim 28, Wahab discloses sustained release injectable microspheres of the anti-inflammatory drug meloxicam which include the biodegradable polymers poly lactide co-glycolide (PLGA) and poly-ε-caprolactone (PCL) (see entire document, particularly “Abstract”). The microspheres were suspended in phosphate buffered saline (a pharmaceutically-acceptable solvent) (“Drug Release Study” at pg. 39).
The limitation of instant claim 28, “wherein the injectable composition will form a solid biodegradable drug depot following a parenteral administration of the injectable composition to a subject in need and the solid biodegradable drug depot provides for the prolonged release of the NSAID for at least one day after administration of the injectable composition” is directed to a future intended use of the composition and properties which occur upon carrying out the intended use. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. As set forth above, Wahab discloses compositions which anticipate the structural components of the instant claim. Per MPEP 2112.01 I., “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).” and further per MPEP 2112.01 II., "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”
Nevertheless, Wahab further discloses that the meloxicam-loaded biodegradable microspheres achieved therapeutic meloxicam levels for 21 successive days following intramuscular injection (“Animals” at pg. 39 and “Conclusion” at pg. 44). As defined in the instant specification (paragraph [0065]), parenteral administration is inclusive of intramuscular injection. Thus, the formulations of Wahab are capable of forming a solid biodegradable drug depot which provides for the release of meloxicam for at least one day following parenteral administration.
Regarding instant claim 33, the PLGA of Wahab is disclosed to have a MW of 17000 Da (17 kDa) (“Materials” at pg. 38).
Regarding instant 38, as set forth above, Wahab discloses suspensions in phosphate buffered saline (“Drug Release Study” at pg. 39), which includes a buffer. Wahab further exemplifies microspheres comprising gelatin or PVA (Tables 1 and 2 at pg. 40), which are taught to act as emulsion stabilizers (“Morphology” at pg. 39).
Regarding instant claim 41, as set forth above, the formulations of Wahab include meloxicam (see entire document, particularly Abstract).
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.
Claims 28, 30-32, 36-39, and 41 are rejected under 35 U.S.C. 103 as being unpatentable over Soll et al. (US 2007/0042013 A1, published February 22, 2007), hereafter “Soll”.
Regarding instant claim 28, Soll teaches long-acting injectable formulations for combatting ectoparasites and/or endoparasites in a mammal comprising a therapeutically effective amount of at least one bioactive agent, a subcutaneously volatile solvent, and a biologically acceptable polymer (see entire document, particularly Abstract and claim 1). Classes of bioactive agents include nonsteroidal anti-inflammatory drugs (NSAIDs) (paragraph [0004]), including COX-2 inhibitors such as meloxicam (paragraph [0129]). Poly(lactide-co-glycolide )copolymer ("PLGA") is highly advantageous as the biologically acceptable polymer (paragraph [0636]; PLGA is also used in example formulations at, for example, paragraphs [0661]-[0663] and [0699]-[0711]). The formulations of Soll are taught to have a therapeutic effect for a period of time of at least about four months (claim 7).
Regarding instant claim 30, Soll teaches that an advantageous form of the injectable formulation is where the bioactive agent is present in an amount of about 0.1 to about 10.0% w/v (paragraph [0638]), overlapping the claimed range. Per MPEP 2144.05 I., “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”.
Regarding instant claims 31-32, Soll teaches that in an advantageous embodiment, when the bioactive polymer is PLGA, the ratio of PL to GA is about 60:40 to about 99:1, or about 75:25 (paragraph [0637]).
Regarding instant claims 36-37, Soll teaches that, advantageously, the subcutaneously volatile solvent is selected from the group including N-methyl-pyrrolidone (NMP) (paragraph [0635]; NMP is also used in example formulations at paragraphs [0699], [0701], and [0703]).
Regarding instant claim 38, Soll teaches that the formulation may optionally include at least one anti-ectoparasitically or anti-endoparasitically acceptable additive, excipient or mixtures thereof and may optionally include an antioxidant (claim 1).
Regarding instant claim 39, as noted above, Soll teaches the inclusion of at least one bioactive agent (claim 1), and suggests combinations of bioactive agents (paragraph [0078]). Examples of bioactive agents include peptides and proteins (paragraph [0630]).
Regarding instant claim 41, as noted above, Soll teaches that bioactive agents includes NSAIDs such as meloxicam (paragraphs [0004] and [0129]).
Soll does not teach the claimed injectable composition with sufficient specificity to anticipate, but rather renders obvious the instant claims.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to combine the prior art elements taught Soll according to known methods to yield predictable results. Here, as described above, Soll teaches long-acting injectable formulations for combatting ectoparasites and/or endoparasites in a mammal comprising the bioactive agent meloxicam, the advantageous inclusion of PLGA and n-methyl-pyrrolidone, the inclusion of excipients such as antioxidants, and the inclusion of multiple bioactive agents including peptides or proteins. Rearrangement of the prior art elements taught by Soll to reach the formulation of the instant claims is within the purview of a person of ordinary skill in the art who is not an automaton and would predictably result in a long-acting injectable formulation capable of combatting ectoparasites and/or endoparasites. Further, per MPEP 2141 I., "[I]n Sakraida v. AG Pro, Inc., the Court derived . . . the conclusion that when a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious." Id. at 417, 82 USPQ2d at 1395-96 (Internal quotations omitted.)”.
The limitation of instant claim 28, “wherein the injectable composition will form a solid biodegradable drug depot following a parenteral administration of the injectable composition to a subject in need and the solid biodegradable drug depot provides for the prolonged release of the NSAID for at least one day after administration of the injectable composition” is directed to a future intended use of the composition and properties which occur upon carrying out the intended use. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art is capable of performing the intended use, then it meets the claim.
As set forth above, the prior art of Soll renders obvious the structural components of the instant claim and arrives at a long-acting injectable composition which has a therapeutic effect from at least about four months (claim 7). The composition of Soll is administered subcutaneously (paragraph [0655]); as defined in the instant specification (paragraph [0065]), parenteral administration is inclusive of subcutaneous injection. Soll further teaches that the subcutaneously volatile solvent dissolves the polymer and bioactive agent prior to injection, then dissipates upon injection and allows for distribution of the agent within the matrix of the polymer (paragraph [0031]). Thus, the composition of Soll is capable of performing the recited intended use, absent evidence to the contrary. See also MPEP 2112.01 II. "A chemical composition and its properties are inseparable.”
Claim 29 is rejected under 35 U.S.C. 103 as being unpatentable over Soll as applied to claim claims 28, 30-32, 36-39, and 41 above, and further in view of Shively et al. (“Physico-chemical characterization of a polymeric injectable implant delivery system” Journal of Controlled Release 1995, 33, 237-243), hereafter “Shively”.
The teachings of Soll are described above.
Soll does not teach that the composition comprises 30-40% by weight of the biodegradable polymer (instant claim 29).
Shively teaches an investigation of the physico-chemical properties of an injectable polymeric implant system to understand in vivo drug release; particularly, Shively teaches drug release from formulations of poly(DL-lactide-co-glycolides) (PLG) and n-methyl-pyrrolidone (see entire document, particularly “Abstract” and “2. Materials and Methods”). Shively teaches that release of a model drug as a function of polymer concentration was evaluated, and the initial drug release comprising 57% PLG was significantly lower than that released from formulations comprising 35% PLG (pg. 242, column 1, paragraph 3 and Figure 5); formulations with polymer concentrations below the precipitation threshold of 40% w/w polymer exhibited approximately twice the initial release compared to formulations above the threshold (Abstract). Shively further teaches that polymer concentration determines the quantity of water required for precipitation or implant formation, which has important implications with regard to the design of appropriate in vitro methods; below 35% w/w, the formation of an implant may be dependent on the rate of fluid flow (see paragraph bridging pgs. 241 and 242 and Figures 3-4).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to routinely optimize the amount of PLGA in the composition of Soll to reach a concentration of the instant claim, as suggested by Shively, who exemplifies polymers at 35 w/w%, and suggests polymer concentrations below 40% w/w, consistent with the claimed range. One of ordinary skill in the art would be motivated to optimize the concentration of polymer in order to achieve the desired initial drug release rate and water required for implant formation, as suggested by Shively. There is a reasonable expectation of success as Soll similarly teaches long-acting injectable compositions comprising poly(lactide-co-glycolide )copolymer and N-methyl-pyrrolidone for prolonged delivery of a drug, and Soll suggests it is advantageous to develop a formulation that does not solidify prior to injection (see paragraphs [0018]-[0022] and [0031]).
Further, per MPEP 2144.05 I., “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)” and per MPEP II. A., “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature 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)”.
Claim 33 is rejected under 35 U.S.C. 103 as being unpatentable over Soll as applied to claims 28, 30-32, 36-39, and 41 above, and further in view of Xu et al. (“Polymer degradation and drug delivery in PLGA-based drug-polymer applications: A review of experiments and theories” Journal of Biomedical Materials Research B: Applied Biomaterials 2017, 105B(6), 1692-1716), hereafter “Xu”.
The teachings of Soll are described above.
Soll does not teach that the biodegradable polymer has an average molecular weight of at least 10 kDa (instant claim 33).
Xu teaches that poly(lactic-co-glycolic acid) (PLGA) copolymers have been broadly used in controlled drug release applications, and that a variety of factors impact the degradation rates of PLGA and concurrent drug release kinetics (see entire document, particularly “Abstract”). Xu teaches that the molecular weight of PLGA significantly influences the physicochemical properties and that a molecular weight of between 5 and 150 kDa is typically used in controlled release applications (“Molecular weight (Mw)” at pg. 1697-1698). It is generally observed that the degradation and drug release increase with decreasing PLGA molecular weight; examples show that initial burst amount can be increased by as much as 8.5 times by controlling Mw (33 kDa compared to 84 kDa) and that the drug release amount in 18 days can change from 95 to 26 wt % when the Mw changes from 14.5 to 213 kDa (“Molecular weight (Mw)” at pg. 1697-1698).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to routinely optimize the molecular weight of PLGA in the composition of Soll within the range of between 5 and 150 kDa, taught by Xu to be typical for PLGA used in controlled release applications, and achieve the molecular weight of the instant claim. One of ordinary skill in the art would be motivated to optimize the molecular weight in order to achieve a desired initial drug burst amount and to control the amount of drug released over time, particularly as Xu suggests that higher molecular weights result in a slower degradation of PLGA and a smaller percentage of drug released. There is a reasonable expectation of success as Soll similarly teaches long-acting compositions comprising PLGA for prolonged delivery of a drug, and that formulations can have a therapeutic effect for at least four months, and up to a year (claim 7).
Further, per MPEP 2144.05 I., “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)” and per MPEP II. A., “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature 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)”.
Independent claim 47 is rejected under 35 U.S.C. 103 as being unpatentable over Soll et al. (US 2007/0042013 A1, published February 22, 2007), hereafter “Soll” in view of Shively et al. (“Physico-chemical characterization of a polymeric injectable implant delivery system” Journal of Controlled Release 1995, 33, 237-243), hereafter “Shively”.
Soll teaches long-acting injectable formulations for combatting ectoparasites and/or endoparasites in a mammal comprising a therapeutically effective amount of at least one bioactive agent, a subcutaneously volatile solvent, and a biologically acceptable polymer (see entire document, particularly Abstract and claim 1). Additional components such as additives, excipients, and antioxidants are recited to be optional, and are thus not required by the formulations of Soll. The formulations of Soll are taught to have a therapeutic effect for a period of time of at least about four months (claim 7).
Classes of bioactive agents include nonsteroidal anti-inflammatory drugs (NSAIDs) (paragraph [0004]), including COX-2 inhibitors such as meloxicam (paragraph [0129]). Soll teaches that an advantageous form of the injectable formulation is where the bioactive agent is present in an amount of about 0.1 to about 10.0% w/v, overlapping the claimed range. Per MPEP 2144.05 I., “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”. Poly(lactide-co-glycolide )copolymer ("PLGA") is highly advantageous as the biologically acceptable polymer (paragraph [0636]; PLGA is also used in example formulations at, for example, paragraphs [0661]-[0663] and [0699]-[0711]); in an advantageous embodiment, when the bioactive polymer is PLGA, the ratio of PL to GA is about 60:40 to about 99:1, or about 75:25 (paragraph [0637]). Soll further teaches that, advantageously, the subcutaneously volatile solvent is selected from the group including N-methyl-pyrrolidone (paragraph [0635]; NMP is also used in example formulations at paragraphs [0699], [0701], and [0703]).
Soll does not teach the limitation that the composition comprises 30-40% of the biodegradable polymer.
Shively teaches an investigation of the physico-chemical properties of an injectable polymeric implant system to understand in vivo drug release; particularly, Shively teaches drug release from formulations of poly(DL-lactide-co-glycolides) (PLG) and n-methyl-pyrrolidone (see entire document, particularly “Abstract” and “2. Materials and Methods”). Shively teaches that release of a model drug as a function of polymer concentration was evaluated, and the initial drug release comprising 57% PLG was significantly lower than that released from formulations comprising 35% PLG (pg. 242, column 1, paragraph 3 and Figure 5); formulations with polymer concentrations below the precipitation threshold of 40% w/w polymer exhibited approximately twice the initial release compared to formulations above the threshold (Abstract). Shively further teaches that polymer concentration determines the quantity of water required for precipitation or implant formation, which has important implications with regard to the design of appropriate in vitro methods; below 35% w/w, the formation of an implant may be dependent on the rate of fluid flow (see paragraph bridging pgs. 241 and 242 and Figures 3-4).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to routinely optimize the amount of PLGA in the composition of Soll to reach a concentration of the instant claim, as suggested by Shively, who exemplifies polymers at 35 w/w%, and suggests polymer concentrations below 40% w/w, consistent with the claimed range. One of ordinary skill in the art would be motivated to optimize the concentration of polymer in order to achieve the desired initial drug release rate and water required for implant formation, as suggested by Shively. There is a reasonable expectation of success as Soll similarly teaches long-acting injectable compositions comprising poly(lactide-co-glycolide )copolymer and N-methyl-pyrrolidone for prolonged delivery of a drug, and Soll suggests it is advantageous to develop a formulation that does not solidify prior to injection (see paragraphs [0018]-[0022] and [0031]).
Further, per MPEP 2144.05 I., “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)” and per MPEP II. A., “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature 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)”.
The limitation “wherein the injectable composition will form a solid biodegradable drug depot following a parenteral administration of the injectable composition to a subject in need and the solid biodegradable drug depot provides for the prolonged release of the NSAID for at least one day after administration of the injectable composition” is directed to a future intended use of the composition and properties which occur upon carrying out the intended use. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art is capable of performing the intended use, then it meets the claim.
As set forth above, the prior art of Soll in view of Shively renders obvious the structural components of the instant claim and arrives at a long-acting injectable composition which has a therapeutic effect from at least about four months (claim 7). The composition of Soll is administered subcutaneously (paragraph [0655]); as defined in the instant specification (paragraph [0065]), parenteral administration is inclusive of subcutaneous injection. Soll further teaches that the subcutaneously volatile solvent dissolves the polymer and bioactive agent prior to injection, then dissipates upon injection and allows for distribution of the agent within the matrix of the polymer (paragraph [0031]). Thus, the composition of the modified Soll is capable of performing the recited intended use, absent evidence to the contrary. See also MPEP 2112.01 II. "A chemical composition and its properties are inseparable.”
Conclusion
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bethany Barham can be reached at (571)272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611
/J.M.K./Examiner, Art Unit 1611
Prosecution Insights