Patent Application 17126748 - SUSTAINED RELEASE COMPOSITIONS USING WAX-LIKE

Title: SUSTAINED RELEASE COMPOSITIONS USING WAX-LIKE MATERIALS

Application Information

Invention Title: SUSTAINED RELEASE COMPOSITIONS USING WAX-LIKE MATERIALS
Application Number: 17126748
Submission Date: 2025-04-09T00:00:00.000Z
Effective Filing Date: 2020-12-18T00:00:00.000Z
Filing Date: 2020-12-18T00:00:00.000Z
National Class: 424
National Sub-Class: 451000
Examiner Employee Number: 85369
Art Unit: 1619
Tech Center: 1600

Rejection Summary

102 Rejections: 0
103 Rejections: 1

Cited Patents

The following patents were cited in the rejection:

US 4166107🔗
US 0113469🔗

Office Action Text

DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Formal Matters
Applicant’s amendments and arguments filed on December 19, 2024 are acknowledged and have been fully considered. Claims 1-21 are pending. Claims 1-3, 6-15, and 21 are under consideration in the instant office action. Claims 4-5, and 16-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claims. Applicant’s claim amendment necessitated a new ground of rejections under 35 USC 112 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Withdrawn Objections/Rejections
Rejections and/or objections not reiterated from the previous office actions are hereby withdrawn as are those rejections and/or objections expressly stated to be withdrawn.
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.

Claims 1-3, 6-15, and 21 are 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.
Instant claim 1 by amendment recites “…, which duration is selected from the group consisting of 1, 2, or 3 days.”
A Markush grouping is a closed group of alternatives, i.e., the selection is made from a group "consisting of" (rather than "comprising" or "including") the alternative members. Abbott Labs., 334 F.3d at 1280, 67 USPQ2d at 1196. The recitation “which duration is selected from the group consisting of 1, 2, or 3 days.” is not a closed group of alternatives. It should be written as “which duration is selected from the group consisting of 1, 2, and 3 days.”

Claims 2-3, 6-15, and 21 are added in the rejection for depending from an indefinite independent claim.
Rejections Maintained
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained through the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.

This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness
Claims 1-3, 6-15, and 21 remain rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over LUKAS (WO 2006/045152, previously cited), Ortyl et al. (US Patent No. 5,738,872, previously cited), Miller et al. (US 4166107, previously cited).
Note: The claims are examined limiting the composition to the elected species active only.
Applicant Claims
Applicant claims a feed-through sustained-release insecticide composition comprising the ingredients in amounts as recited.
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
LUKAS teaches a process for producing a compressed solid dosage form containing an active ingredient. The process includes a step of preparing core elements containing the active ingredient. Optionally the core elements are coated with a pharmaceutically acceptable coating layer to form coated pellets. The core elements or pellets are treated with an anti-static agent and compressed with suitable excipients to form the compressed solid dosage form. Preferred anti-static agents are starch, microcrystalline cellulose, kaolin, bentonite, silicates, silicon dioxide, cellulose, stearic acid, sodium stearyl fumarate and glyceryl behenate (see abstract). The present invention is primarily concerned with compressed solid dosage forms such as tablets. A build up of static charge is a significant problem during tablet formation using the processes just described. The build up of static charge during core element or pellet formation can interfere with handling and processing of the core elements or pellets. For example, it is generally necessary to remove both over and under size pellets by sieving, and a build up of static charge can interfere with the flowability of the core elements or pellets being sieved. It is also important that the flow of core elements or pellets between a hopper containing the core elements or pellets and a tablet press is uniform and predictable and a build up of static charge can interfere with that flow (see pages 1-2). The present invention provides processes for producing core elements and pellets that can be used to form tablets but which reduce problems associated with a build up of static charge during core element and pellet formation and subsequent processing. The processes of the invention do not adversely affect tablet formation (see page 2). A process for producing a compressed solid dosage form containing an active ingredient, the process including:
- preparing core elements containing the active ingredient,
- optionally coating the core elements with a pharmaceutically acceptable coating layer to form coated pellets,
- treating the core elements or pellets with an anti-static agent, and
- compressing the treated core elements or pellets with suitable excipients to form the compressed solid dosage form, wherein the hardness of the compressed solid dosage form is greater for a given compression force than an equivalent solid dosage form in which the core elements or pellets have been treated with talc (see claim 1). In a preferred form of the invention, the anti-static agent is admixed with the core elements or pellets in particulate form. Most preferably, the anti-static agent is in powdered form. The anti-static agent may be added manually or it may be added in an air stream. In the case of a powdered anti-static agent, the step of treating the core elements or pellets with the anti-static agent may also be referred to as dusting the core elements or pellets (see page 4). The anti-static agent used in the process of the present invention may be any inorganic or organic solid that reduces static but still allows cohesion between core elements or pellets and excipients in the solid dosage form in order for it to retain strength and structure. Materials having anti-static properties may be in a powdered form (i.e. a particle size less than about 250 microns) and be pharmaceutically acceptable. Examples of suitable materials may include, but not be limited to, polysaccharides, minerals, clays, organic acids, silicates, silicon dioxide, stearates, fumarates, and glyceryl esters. Preferably, the anti-static agent is selected from the list including starch, microcrystalline cellulose, kaolin, bentonite, magnesium trisilicate, aluminium trisilicate, silicon dioxide, cellulose, stearic acid, sodium stearyl fumarate, and glyceryl behenate (see page 4). The term "active ingredient" will be widely understood and denotes a compound having a beneficial effect when introduced into a system such as a biological system. For example, the active ingredient may be a biologically active compound for introduction into a human, animal, plant, water body or soil strata. Examples of biologically active compounds for this purpose include pharmaceutically active ingredients and agrochemicals. Exemplary agrochemicals include fertilisers, nutrients, pesticides, fungicides and algaecides. Pharmaceutically active ingredients include any compound that provides prophylactic and/or therapeutic properties when administered to, for example, humans. Examples include, but are not limited to, pharmaceutical actives, therapeutic actives, veterinarial actives, nutraceuticals, and growth regulators. Reference in this specification to a specific active ingredient is also to be understood to include the active ingredient in the form of acid addition salts, solvates, hydrates and the like (see pages 6-7). As used herein, the term "core element" will be understood to mean un-coated particles containing a mixture of one or more active ingredients and excipients. These may be produced by, for example, granulation or spray drying of mixtures of active ingredients and excipients, or by applying a layer of the active ingredient over inert cores. The term "pellets" as used herein will be understood to mean coated core elements. Typically, the coating will be a modified release coating. It will be appreciated that the process of the present invention may be applied to core elements and/or pellets (see page 7). As described previously, the present invention provides a process for producing compressed solid dosage forms containing an active ingredient. To produce compressed solid dosage forms, such as tablets, a mixture containing an active ingredient (eg. a drug) and excipients may be granulated to form core elements. The granulation process may be a "wet granulation" process which means that water or other solvent is used in the granulation step. An alternative process for producing a core element is to apply a layer of active ingredient over inert cores. The layer of active ingredient may be applied by spraying a solution of the active ingredient onto the inert cores. A drying step may be used to remove some or all of the solvent from the core element (see page 8). The core elements formed by either of these processes may be incorporated directly into a solid dosage form or they may first be coated with a pharmaceutically acceptable coating layer to form pellets. This coating step may be performed to confer controlled release or other properties onto the pellets. Thus, the core elements to be coated may be suspended in an air stream while a coating material (usually dissolved or suspended in a suitable liquid vehicle or solvent) is atomised onto the core elements to form the coated pellets. . A drying step may be used to remove some or all of the solvent from the pellets. The core elements or pellets thus formed are then incorporated into the solid dosage form. In the case of a tablet, they may be blended with tablet excipients and then pressed into the form of a tablet. The core elements or pellets are preferably treated with an anti-static agent at or after a drying step to reduce accumulated static charge or to prevent or reduce accumulation of static charge (see page 8). The first step in the process of the present invention is the preparation of core elements containing the active ingredient. In a preferred embodiment, this involves a process of granulation, extrusion, and marumerisation using the active ingredient and suitable excipients to form a plurality of core elements containing the active ingredient. An alternative is to apply a layer of the active ingredient onto inert cores to form core elements containing the active ingredient. To form the core elements consecutive steps of wet granulation, extrusion and marumerisation are described herein (see Example 1 ). However, the person skilled in the art will appreciate that any of a number of techniques may be used, such as spheronisation onto seed cores, or rotogranulation (see page 9). The active ingredient may be present in the core element in any suitable amount, and for instance may be provided in an amount from 5 to 95% by weight, preferably from 20 to 80% by weight, based on the total weight of the core element. The active ingredient may be embodied within and through the core element, combined with or without the normal excipients, additives and fillers. Preferably, the core elements each have a diameter in the range of 50 microns to 1700 microns. In one particularly preferred form of the invention the core elements each have a diameter in the range of 500 microns to 1000 microns. The core elements may contain any suitable or required additives, such as excipients, fillers or other ingredients. For example, modified release core elements may be formed by granulating the active ingredient with insoluble materials such as waxes or insoluble polymers (see page 10). The core elements may be coated with a coating to form pellets. A coating may be applied for a number of reasons, such as, masking a bitter taste, or altering the rate of release (dissolution) of the active ingredient. Preferably, the core elements are coated to provide a modified release profile. The modified release coating may be any suitable coating material, or combination of coating materials, that will provide a desired modified release profile. For example, coatings such as enteric coatings, semi-enteric coatings, delayed release coatings or pulsed release coatings may be desired. A mixture of enteric polymers may be used to produce a modified release coating. It is possible to use a mixture of enteric polymer with a water permeable, water swellable or water-soluble material such as polyvinylpyrrolidone, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyethylene glycol having a molecular weight of from 1700 to 20,000, or a mixture thereof. The coating could also be a water- insoluble material, such as ethylcellulose, and/or enteric polymers such as cellulose acetate phthlate, hydroxypropyl methylcellulose phthalate (HPMCP), polyvinyl acetate phthalate, methacrylic acid copolymer, hydroxypropyl methylcellulose acetate succinate, shellac, cellulose acetate trimellitate, or a mixture thereof. In particular, materials such as hydroxypropylmethyl cellulose, hydroxypropylmethyl cellulose phthalate of varying grades and also as an aqueous dispersion, Eudragit® L100-55, Eudragit® L30D, and hydroxypropylmethyl cellulose acetate succinate may be used to form the modified release coating. The coating may also contain plasticisers such as triethyl citrate, diethyl phthalate or dibutyl sebacate (see page 11). Either during or directly after either of the aforementioned drying steps, the core elements or pellets are treated with an anti-static agent, such as starch or magnesium trisilicate, to reduce accumulated static charge or to prevent or reduce accumulation of static charge during processing and handling of the core elements or pellets. The anti-static agent is an organic or inorganic solid that reduces static without substantially affecting compressibility of a blend containing core elements or pellets to which it has been added. Preferably, the anti-static agent is selected from the list including starch, microcrystalline cellulose, kaolin, bentonite, silicates (such as magnesium trisilicate and aluminium trisilicate), silicon dioxide, cellulose, stearic acid, sodium stearyl fumarate, and glyceryl behenate (see page 12). After formation and treatment with an anti-static agent, the core elements or pellets are passed through sieves to obtain core elements or pellets of defined size range. A relatively narrow size range is desirable when a uniform rate of drug release is desirable. It depends on the individual situation, but generally, coated pellets in the range 50 microns to 2000 microns, preferably 500 to 1180 microns are desired (see page 13). Suitable tabletting excipients will be known to a person skilled in the art. The person skilled in the art will also appreciate that the proper formulation of a tablet involves balancing the need for content uniformity (i.e. making sure the same number of core elements or pellets is present in each tablet and therefore the same amount of active ingredient is present in each tablet) and the friability of any tablet that is formed as well as protection of coated pellets from fracture of the coating during the tabletting step. In this respect, if the weight ratio of core elements or pellets to excipients is too low, there will be problems with content uniformity, while if the weight ratio of core elements or pellets is too high there will not be enough tabletting excipients to cushion the core elements or pellets during compression into a tablet and the structural integrity of the core elements or pellets could be compromised. Also, if the amount of excipients is low the core elements or pellets are more likely to be damaged during compression and the tablets will also be weak and friable because they will not have sufficient binder to hold them together. Therefore the percentage of core elements or pellets in each tablet is ideally in the range of 20 to 50% (more preferably 25 to 35%, but most preferably about 30%) by weight of the total dosage weight (see pages 14-15). It will also be appreciated that the tablets may include a range of traditional additives such as disintegrants, diluents, fillers, lubricants, glidants, colourants and flavours in addition to the anti-static agent used in the treating step. For example, suitable disintegrants may be those that have a large coefficient of expansion, and examples may include crosslinked polymers such as crospovidone (crosslinked polyvinylpyrrolidone) and croscarmellose (crosslinked sodium carboxymethylcellulose). Also, it will be appreciated that it may be advantageous to add to a dosage form an inert substance such as a diluent or filler. A variety of materials may be used as diluents or fillers, and examples may be lactose, starch, sucrose, dextrose, mannitol, sorbitol, microcrystalline cellulose, and others known in the art, and mixtures thereof. Lubricants and glidants may be employed in the manufacture of certain dosage forms, and will usually be employed when producing tablets. Examples of lubricants and glidants are hydrogenated vegetable oils, magnesium stearate, stearic acid, sodium lauryl sulfate, magnesium lauryl sulfate, colloidal silica, talc, mixtures thereof, and others known in the art. Additives such as colouring agents and pigments may also be added to dosage forms in accordance with the present invention, and suitable colouring agents and pigments may include titanium dioxide and dyes suitable for food. The strength of the tablet of the present invention (measurement with a tablet hardness tester) is usually about 1 to 20 kiloponds (kp), preferably about 5 to 15 kp, more preferably 7 to 15 kp, although it will be appreciated that these hardness values are dependent to some extent on the physical dimensions of the tablet (see pages 15-16).
Ascertainment of the Difference between Scope the Prior Art and the Claims
(MPEP §2141.012)
LUKAS does not explicitly teach pregelatinized starch and its amounts and the amounts of microcrystalline cellulose. These deficiencies are cured by the teachings of Ortyl et al.
Ortyl et al. teach a pharmaceutical composition in solid unit dosage form, comprising, a) a therapeutically effective amount of a piperidinoalkanol compound or a pharmaceutically acceptable salt thereof; and, b) at least one inert ingredient (see abstract). Efforts have focused on improving the bioavailability of various piperidinoalkanol compounds in order to improve their therapeutic efficiency. The present invention relates to pharmaceutical compositions and pharmaceutical compositions in solid unit dosage form wherein the piperidinoalkanol compound, or a pharmaceutically acceptable salt thereof, is in combination with inert ingredients (column 1, lines 45-52). As used herein the term "inert ingredient" refers to those therapeutically inert ingredients that are well known in the art of pharmaceutical science which can be used singly or in various combinations, and include, for example, binders, diluents, lubricants, glidants, sweetening agents, disintegrants, coloring agents, flavoring agents, antioxidants, solubilizing agents, coating agents and the like, as are disclosed in The United States Pharmacopeia, XXII, 1990, (1989 The United States Pharmacopeial Convention, Inc.), pages 1857-1859, which is incorporated herein by reference. For example, the following inert ingredients can be utilized singly or in various combinations; binders such as gelatin, polyvinylpyrrolidone (PVP), pregelatinized starch, povidone, cellulose derivatives including methyl cellulose, carboxymethyl cellulose, hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), sucrose and the like; diluents such as calcium carbonate, lactose, starch, microcrystalline cellulose, and the like; lubricants such as magnesium stearate, calcium stearate, zinc stearate, stearic acid, talc, hydrogenated vegetable oil and the like; glidants such as silicon dioxide, talc and the like; disintegrants such as alginic acid, methacrylic acid DVB, cross-linked PVP, microcrystalline cellulose, croscarmellose sodium, crospovidone, polacrilin potassium, sodium starch glycolate, starch, pregelatinized starch and the like; preferred disintegrants are croscarmellose sodium, starch, pregelatinized starch and sodium starch glycolate with croscarmellose sodium being the most preferred disintegrant; sweetening agents; coloring agents; flavoring agents; antioxidants; and the like. The above inert ingredients can be present in amounts up to about 95% of the total composition weight (column 13, lines 15-46).
A suitable combination of inert ingredients comprises microcrystalline cellulose, pregelatinized starch, gelatin, magnesium stearate, calcium carbonate and sodium starch glycolate, in amounts of from about 20% to about 85%, 5% to about 50%, 1% to about 15%, 0.05% to about 3%, 5% to about 50%, and 1% to about 15%. A preferred combination of inert ingredients is microcrystalline cellulose, pregelatinized starch, calcium carbonate, magnesium stearate and sodium starch glycolate in amounts of from about 20% to about 85%, 5% to about 50%, 5% to about 50%, 0.05% to about 3%, and 1% to about 15%. Another preferred combination of inert ingredients comprises: microcrystalline cellulose, pregelatinized starch, magnesium stearate, and croscarmellose sodium in amounts of from about, 20% to about 85%, 5% to about 50%, 0.05 to about 3%, 1% to about 10%. The most preferred combination of inert ingredients is croscarmellose sodium, microcrystalline cellulose, lactose, pregelatinized starch and gelatin, in amounts of from about 1% to about 10%, 20% to about 85%, 20% to about 85%, 1% to about 30% and 1% to about 15% respectively. The most especially preferred combination of inert ingredients is croscarmellose sodium, microcrystalline cellulose, lactose, pregelatinized starch, gelatin and magnesium stearate, in amounts of from about 1% to about 10%, 20% to about 85%, 20% to about 85%, 1% to about 30%, 1% to about 15% and 0.05% to about 3% respectively. The following entries 1 through 7 in Table 5, provide the most preferred amounts of the respective inert ingredients which can be utilized in preparation of the tablet or capsule dosage forms (column 13, lines 47-67 and column 14, lines 1-8).

LUKAS and Ortyl et al. do not specifically teach Methoprene as the active ingredient. This deficiency is cured by Miller et al.
Miller et al. teach compositions of insect regulators comprising monostearin, carnuba wax, barium sulfate, methoprene, and diflubenzuron are selectively formulated into a sustained-release bolus and orally administered to livestock to control the larvacidal activity of arthropods in the manure of the livestock (see abstract). A sustained release bolus formulation for the control of arthropods in cattle manure, said formulation comprising the following composition: about 4-17 parts monostearin, about 4-10 parts carnuba wax, about 70-75 parts Barium Sulfate, and about 1-15 parts Methoprene (claim 1). Repeated treatment of livestock is expensive in terms of both labor and insecticide. To compensate for rapid degradation of the pesticides on animals, the producer must apply larger quantities than are necessary for control of the immediate population if toxic levels are to be maintained for any length of time. Such a practice is wasteful of insecticide, results in greater contamination to the environment, and increases the probability of toxicity to animals and of residues in animal products. Therefore, one of the objectives of studies conducted at the U.S. Livestock Insects Laboratory, Kerrville, Tex., is to develop techniques that will make it possible to maintain the minimum effective level of toxicant on livestock over an extended period and thereby to increase the efficacy, efficiency, and safety of livestock pest control. This report deals with our efforts to use controlled-release technology against horn flies, Haematobia irritans (L.), common cattle grubs, Hypoderma lineatum (De Villers), and face fly, Musca autumnalis (DeGeer). Boluses have been used in veterinary medicine to provide nutritional and therapeutic substances to animals for predetermined periods. But, for several reasons the technique has not been used in the control of livestock pests: (1) the effective dose of most conventional insecticides is usually too large for the bolus form to be practical; (2) many insecticides are degraded by the digestive processes of the animal and by the environment; and (3) conventional insecticides can accumulate in animal tissues and thereby produce objectionable residues. However, insect growth regulators (IGR's) are chemicals of another type and might be more acceptable in a bolus than conventional insecticides. Insect growth regulators have been used successfully in the control of dung breeding pests of cattle for several years. Complete inhibition of development in manure has been achieved by administering insect growth regulators (IGR) to cattle in ground feed (Harris et al, 1973), in mineral blocks (Harris et al, 1974) and in drinking water (Beadles et al, 1975; Miller et al, 1976, 1977). Free-choice consumption and the resultant variations in dosage are inherent problems in the practical application of any of these techniques. Additionally, in some areas, animals will not consume supplemental minerals since their mineral requirements are amply met by the natural diet. The presence of untreatable sources of water (streams, rainfall) can interfere with the use of a water treatment. The use of sustained-release bolus formulations is another approach to supplying animals with small daily dosages of materials. Boluses have been used in animal husbandry to provide nutritional and therapeutic substances such as trace elements, antibiotics, anthelmintics, animal hormones, and growth stimulants over predetermined periods of time. The prior art for these dosages forms is adequately described in patent literature such as, for example, U.S. Pat. No. 3,056,724 (Marston 1962), U.S. Pat. No. 3,507,952 (Rednick and Tucker 1970) and U.S. Pat. No. 3,535,419 (Siegrist and Katz 1970). However, bolus dosage forms have not been used in the control of livestock arthropods because the effective dosage of most conventional insecticides is usually too large to make the bolus form practical, many insecticides are destroyed by digestive process and environment, and conventional insecticides are often accumulated in animal tissues and, thereby produce undesirable residues. The use of sustained-release bolus formulations to administer insect growth regulators for the control of livestock pests overcomes many of the aforementioned problems associated with ad lib treatments. Additionally, the efficacy and relative safety to insect growth regulators enables the use of the bolus treatment for long-lasting control measures (see entire column 1 and 2).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious to one of ordinary skill in the art at the time the claimed invention was made to modify the teachings of LUKAS via incorporating pregelatinized starch and microcrystalline cellulose in amounts as recited because Ortyl et al. teach a pharmaceutical composition in solid unit dosage form, comprising, a) a therapeutically effective amount of a piperidinoalkanol compound or a pharmaceutically acceptable salt thereof; and, b) at least one inert ingredient (see abstract). Efforts have focused on improving the bioavailability of various piperidinoalkanol compounds in order to improve their therapeutic efficiency. The present invention relates to pharmaceutical compositions and pharmaceutical compositions in solid unit dosage form wherein the piperidinoalkanol compound, or a pharmaceutically acceptable salt thereof, is in combination with inert ingredients (column 1, lines 45-52). As used herein the term "inert ingredient" refers to those therapeutically inert ingredients that are well known in the art of pharmaceutical science which can be used singly or in various combinations, and include, for example, binders, diluents, lubricants, glidants, sweetening agents, disintegrants, coloring agents, flavoring agents, antioxidants, solubilizing agents, coating agents and the like, as are disclosed in The United States Pharmacopeia, XXII, 1990, (1989 The United States Pharmacopeial Convention, Inc.), pages 1857-1859, which is incorporated herein by reference. For example, the following inert ingredients can be utilized singly or in various combinations; binders such as gelatin, polyvinylpyrrolidone (PVP), pregelatinized starch, povidone, cellulose derivatives including methyl cellulose, carboxymethyl cellulose, hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), sucrose and the like; diluents such as calcium carbonate, lactose, starch, microcrystalline cellulose, and the like; lubricants such as magnesium stearate, calcium stearate, zinc stearate, stearic acid, talc, hydrogenated vegetable oil and the like; glidants such as silicon dioxide, talc and the like; disintegrants such as alginic acid, methacrylic acid DVB, cross-linked PVP, microcrystalline cellulose, croscarmellose sodium, crospovidone, polacrilin potassium, sodium starch glycolate, starch, pregelatinized starch and the like; preferred disintegrants are croscarmellose sodium, starch, pregelatinized starch and sodium starch glycolate with croscarmellose sodium being the most preferred disintegrant; sweetening agents; coloring agents; flavoring agents; antioxidants; and the like. The above inert ingredients can be present in amounts up to about 95% of the total composition weight (column 13, lines 15-46). One of ordinary skill in the art would have been motivated to do so because Ortyl et al. teach that a suitable combination of inert ingredients comprises microcrystalline cellulose, pregelatinized starch, gelatin, magnesium stearate, calcium carbonate and sodium starch glycolate, in amounts of from about 20% to about 85%, 5% to about 50%, 1% to about 15%, 0.05% to about 3%, 5% to about 50%, and 1% to about 15%. A preferred combination of inert ingredients is microcrystalline cellulose, pregelatinized starch, calcium carbonate, magnesium stearate and sodium starch glycolate in amounts of from about 20% to about 85%, 5% to about 50%, 5% to about 50%, 0.05% to about 3%, and 1% to about 15%. Another preferred combination of inert ingredients comprises: microcrystalline cellulose, pregelatinized starch, magnesium stearate, and croscarmellose sodium in amounts of from about, 20% to about 85%, 5% to about 50%, 0.05 to about 3%, 1% to about 10%. The most preferred combination of inert ingredients is croscarmellose sodium, microcrystalline cellulose, lactose, pregelatinized starch and gelatin, in amounts of from about 1% to about 10%, 20% to about 85%, 20% to about 85%, 1% to about 30% and 1% to about 15% respectively. The most especially preferred combination of inert ingredients is croscarmellose sodium, microcrystalline cellulose, lactose, pregelatinized starch, gelatin and magnesium stearate, in amounts of from about 1% to about 10%, 20% to about 85%, 20% to about 85%, 1% to about 30%, 1% to about 15% and 0.05% to about 3% respectively. The following entries 1 through 7 in Table 5, provide the most preferred amounts of the respective inert ingredients which can be utilized in preparation of the tablet or capsule dosage forms (column 13, lines 47-67 and column 14, lines 1-8). It should be noticed that these are conventionally known inert pharmaceutical ingredients that are useful to all classes of actives taught by LUKAS. 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. "Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." 325 U.S. at 335, 65 USPQ at 301.). Furthermore, in the case where the claimed ranges for amount of ingredients and active and also particle sizes “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). Additionally, differences in concentration 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). 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). The skilled artisan would have had a reasonable chance of expectation of success in combining the teachings of LUKAS and Ortyl et al. because both references teach sustained or controlled release delivery of actives through solid dosage forms.
It would have been prima facie obvious to one of ordinary skill in the art at the time the claimed invention was made to modify the sustained (controlled) release dosage form of LUKAS and Ortyl et al. for the delivery of Methoprene because Miller et al. teach compositions of insect regulators comprising monostearin, carnuba wax, barium sulfate, methoprene, and diflubenzuron are selectively formulated into a sustained-release bolus and orally administered to livestock to control the larvacidal activity of arthropods in the manure of the livestock (see abstract). A sustained release bolus formulation for the control of arthropods in cattle manure, said formulation comprising the following composition: about 4-17 parts monostearin, about 4-10 parts carnuba wax, about 70-75 parts Barium Sulfate, and about 1-15 parts Methoprene (claim 1). One of ordinary skill in the art would have been motivated to do so because first LUKAS teach that its formulation is useful to deliver a compound having a beneficial effect when introduced into a system such as a biological system. For example, the active ingredient may be a biologically active compound for introduction into a human, animal, plant, water body or soil strata. Examples of biologically active compounds for this purpose include pharmaceutically active ingredients and agrochemicals. Exemplary agrochemicals include fertilisers, nutrients, pesticides, fungicides and algaecides. Pharmaceutically active ingredients include any compound that provides prophylactic and/or therapeutic properties when administered to, for example, humans. Examples include, but are not limited to, pharmaceutical actives, therapeutic actives, veterinarial actives, nutraceuticals, and growth regulators. Reference in this specification to a specific active ingredient is also to be understood to include the active ingredient in the form of acid addition salts, solvates, hydrates and the like (see pages 6-7). Furthermore, Miller et al. teach that repeated treatment of livestock is expensive in terms of both labor and insecticide. To compensate for rapid degradation of the pesticides on animals, the producer must apply larger quantities than are necessary for control of the immediate population if toxic levels are to be maintained for any length of time. Such a practice is wasteful of insecticide, results in greater contamination to the environment, and increases the probability of toxicity to animals and of residues in animal products. Therefore, one of the objectives of studies conducted at the U.S. Livestock Insects Laboratory, Kerrville, Tex., is to develop techniques that will make it possible to maintain the minimum effective level of toxicant on livestock over an extended period and thereby to increase the efficacy, efficiency, and safety of livestock pest control. This report deals with our efforts to use controlled-release technology against horn flies, Haematobia irritans (L.), common cattle grubs, Hypoderma lineatum (De Villers), and face fly, Musca autumnalis (DeGeer). Boluses have been used in veterinary medicine to provide nutritional and therapeutic substances to animals for predetermined periods. But, for several reasons the technique has not been used in the control of livestock pests: (1) the effective dose of most conventional insecticides is usually too large for the bolus form to be practical; (2) many insecticides are degraded by the digestive processes of the animal and by the environment; and (3) conventional insecticides can accumulate in animal tissues and thereby produce objectionable residues. However, insect growth regulators (IGR's) are chemicals of another type and might be more acceptable in a bolus than conventional insecticides. Insect growth regulators have been used successfully in the control of dung breeding pests of cattle for several years. Complete inhibition of development in manure has been achieved by administering insect growth regulators (IGR) to cattle in ground feed (Harris et al, 1973), in mineral blocks (Harris et al, 1974) and in drinking water (Beadles et al, 1975; Miller et al, 1976, 1977). Free-choice consumption and the resultant variations in dosage are inherent problems in the practical application of any of these techniques. Additionally, in some areas, animals will not consume supplemental minerals since their mineral requirements are amply met by the natural diet. The presence of untreatable sources of water (streams, rainfall) can interfere with the use of a water treatment. The use of sustained-release bolus formulations is another approach to supplying animals with small daily dosages of materials. Boluses have been used in animal husbandry to provide nutritional and therapeutic substances such as trace elements, antibiotics, anthelmintics, animal hormones, and growth stimulants over predetermined periods of time. The prior art for these dosages forms is adequately described in patent literature such as, for example, U.S. Pat. No. 3,056,724 (Marston 1962), U.S. Pat. No. 3,507,952 (Rednick and Tucker 1970) and U.S. Pat. No. 3,535,419 (Siegrist and Katz 1970). However, bolus dosage forms have not been used in the control of livestock arthropods because the effective dosage of most conventional insecticides is usually too large to make the bolus form practical, many insecticides are destroyed by digestive process and environment, and conventional insecticides are often accumulated in animal tissues and, thereby produce undesirable residues. The use of sustained-release bolus formulations to administer insect growth regulators for the control of livestock pests overcomes many of the aforementioned problems associated with ad lib treatments. Additionally, the efficacy and relative safety to insect growth regulators enables the use of the bolus treatment for long-lasting control measures (see entire column 1 and 2). Furthermore, in the case where the claimed ranges for amount of ingredients and active and also particle sizes “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). Additionally, differences in concentration 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). 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). The skilled artisan would have had a reasonable chance of expectation of success in combining the teachings of LUKAS, Ortyl et al., and Miller et al. because all of the references teach sustained or controlled release delivery of actives through solid dosage forms.
With regard to the limitation reciting “…, which duration is selected from the group consisting of 1, 2, or 3 days.”, it should be noticed that both LUKAS and Miller et al. are drawn to controlled or sustained release formulations. Furthermore, the combination teachings of LUKAS, Ortyl et al., and Miller et al. met the claimed composition. Hence, all pharmacokinetic or pharmacodynamic profiles Applicant recites would necessarily be there. “[I]nherency may supply a missing claim limitation in an obviousness analysis." PAR, 773 F.3d at 1194-1195 ; see also Endo Pharms. Sols., Inc. v. Custopharm Inc., 894 F.3d 1374 , 1381 , 127 U.S.P.Q.2D (BNA) 1409 (Fed. Cir. 2018) ("An inherent characteristic of a formulation can be part of the prior art in an obviousness analysis even if the inherent characteristic was unrecognized or unappreciated by a skilled artisan."). It is long settled that in the context of obviousness, the "mere recitation of a newly discovered function or property, inherently possessed by things in the prior art, does not distinguish a claim drawn to those things from the prior art." In re Oelrich, 666 F.2d 578 , 581 (C.C.P.A. 1981). The Supreme Court explained long ago that "[i]t is not invention to perceive that the product which others had discovered had qualities they failed to detect." Gen. Elec. Co. v. Jewel Incandescent Lamp Co., 326 U.S. 242 , 249 , 66 S. Ct. 81 , 90 L. Ed. 43 , 1946 Dec. Comm'r Pat. 611 (1945). We too have previously explained that "an obvious formulation cannot become nonobvious simply by administering it to a patient and claiming the resulting serum concentrations," because "[t]o hold otherwise would allow any formulation—no matter how obvious—to become patentable merely by testing and claiming an inherent property." Santarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344 , 1354 (Fed. Cir. 2012). In In re Kao, we found that the claimed controlled-release oxymorphone formulation was obvious because an inherent pharmacokinetic property of oxymorphone that was present in controlled-release oxymorphone "add[ed] nothing of patentable consequence." In re Huai-Hung Kao, 639 F.3d 1057 , 1070 , 98 U.S.P.Q.2D (BNA) 1799 (Fed. Cir. 2011). In In re Kubin, we found an inherent property obvious, explaining that "[e]ven if no prior art of record explicitly discusses the [limitation], the . . . application itself instructs that [the limitation] is not an additional requirement imposed by the claims on the [claimed protein], but rather a property necessarily present in [the claimed protein]." In re Kubin, 561 F.3d 1351 , 1357 , 90 U.S.P.Q.2D (BNA) 1417 (Fed. Cir. 2009). Our predecessor court similarly concluded that it "is not the law" that "a structure suggested by the prior art, and, hence, potentially in the possession of the public, is patentable . . . because it also possesses an [i]nherent, but hitherto unknown, function which [the patentees] claim to have discovered." In re [*1191] Wiseman, 596 F.2d 1019 , 1023 (C.C.P.A. 1979). Inherency, however, is a "high standard," that is "carefully circumscribed in the context of obviousness." PAR, 773 F.3d at 1195 . Inherency "may not be established by probabilities or possibilities," and "[t]he mere fact that a certain thing may result from a given set of circumstances is not sufficient." Oelrich, 666 F.2d at 581 (emphasis added) (quoting Hansgirg v. Kemmer, 102 F.2d 212 , 214 , 26 C.C.P.A. 937 , 1939 Dec. Comm'r Pat. 327 (C.C.P.A. 1939); see also In re Rijckaert, 9 F.3d 1531 , 1533-1534 (Fed. Cir. 1993). Rather, inherency renders a claimed limitation obvious only if the limitation is "necessarily present," or is "the natural result of the combination of elements explicitly disclosed by the prior art." PAR, 773 F.3d at 119511 -96; see also Alcon Research, Ltd. v. Apotex Inc., 687 F.3d 1362 , 1369 (Fed. Cir. 2012) (relying on inherency where the claims recited "a property that is necessarily present" in the prior art). "If . . . the disclosure is sufficient to show that the natural result flowing from the operation as taught would result in the performance of the questioned function, it seems to be well settled that the disclosure should be regarded as sufficient" to render the function inherent. Oelrich, 666 F.2d at 581 (quoting Hansgirg v. Kemmer, 102 F.2d 212 , 214 , 26 C.C.P.A. 937 , 1939 Dec. Comm'r Pat. 327 (C.C.P.A. 1939)). On appeal, Persion contends that the district court erred in applying the inherency doctrine in its obviousness analysis because Devane does not teach administering its hydrocodone-only formulation to patients with mild or moderate hepatic impairment. Thus, Persion asserts, "'the natural result flowing from the operation as taught' in Devane cannot be the claimed [pharmacokinetic] values for [hepatically impaired] patients." Appellant's Br. 37 (quoting Oelrich, 666 F.2d at 581 ); Reply Br. 19. To the extent Persion contends that inherency can only satisfy a claim limitation when all other limitations are taught in a single reference, that position is contrary to our prior recognition that "inherency may supply a missing claim limitation in an obviousness analysis" where the limitation at issue is "the natural result of the combination of prior art elements." PAR, 773 F.3d at 1194-1195 (emphasis added, internal quotations omitted). Here, the district court specifically found that Devane, together with Jain, the state of the prior art at the time of invention, and the Vicodin and Lortab labels, taught the combination of elements that inherently result in the claimed pharmacokinetic parameters. The district court found that a person of ordinary skill in the art would have been motivated, with reasonable expectation of success, to administer an unadjusted dose of the Devane formulation to hepatically impaired patients. There was also no dispute that the Devane formulation, which was identical to the Zohydro ER formulation described in the patents in suit, necessarily exhibited the claimed parameters under these conditions. Pernix, 323 F. Supp. 3d at 607 , 610 . In this context, the district court did not err by finding that the pharmacokinetic limitations of the asserted claims were inherent and added no patentable weight to the pharmacokinetic claims.
With regard to the preamble recitation “A feed-through sustained-release insecticide composition” it is an intended use limitation. 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 structure is capable of performing the intended use, then it meets the claim.
In light of the forgoing discussion, one of ordinary skill in the art would have concluded that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Applicant’s Arguments
Applicant argues Lukas does not teach methoprene. No where does Lukas teach an insecticide as claimed. The term “growth factor” recited only once in Lukas in no way means an “insect growth regulator” as claimed. In fact, a growth regulator as recited in Lukas means just the opposite of what is being claimed. A growth factor as defined in Wikipedia is as follows:

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In other words, growth factors promote growth. On the other hand, the term an Insect Growth Regulator as claimed disrupts growth. As defined in Wikipedia:

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A person of ordinary skill in the art would not mistake a growth factor as disclosed in Lukas for an insect growth regulator as currently claimed. The former promotes growth whereas the latter disrupts the growth to kill insects. They are simply not the same. MPEP § 2143.03(VI) states that “[a] prior art reference must be considered in its entirety, i.e., as a whole, including portions that would lead away from the claimed invention.” The foregoing portion of Lukas actually leads away from the claimed invention and does not support a prima facie case of obviousness. In addition, the modification of Lukas and the formulation disclosed therein to arrive at a feed-through formulation as claimed would change the principle of operation. “If the proposed modification or combination of the prior art would change the principle of operation of the prior art invention being modified, then the teachings of the references are not sufficient to render the claims prima facie obvious.” Lukas in no way teaches or suggests a feed-through formulation as claimed. /n re Ratti, 270 F.2d 810, 813, 123 USPQ 349, 352 (CCPA 1959); MPEP § 2143.01. Lukas teaches oral administration but does not teach a formulation which is effective outside an animal to be an effective insecticide. As such, such a modification of Lukas would change its principle of operation.
The above assertions are not found persuasive because first the examiner reminds applicant that the rejection is based on the combination teachings of the references not just the teachings of Lukas only. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Second, the examiner also reminds Applicant that a prior art reference must be considered in its entirety, i.e., as a whole, including portions that would lead away from the claimed invention. W.L. Gore & Assoc., Inc. v. Garlock, Inc., 721 F.2d 1540, 220 USPQ 303 (Fed. Cir. 1983), cert. denied, 469 U.S. 851 (1984). Lukas teaches that the term "active ingredient" will be widely understood and denotes a compound having a beneficial effect when introduced into a system such as a biological system. For example, the active ingredient may be a biologically active compound for introduction into a human, animal, plant, water body or soil strata. Examples of biologically active compounds for this purpose include pharmaceutically active ingredients and agrochemicals. Exemplary agrochemicals include fertilisers, nutrients, pesticides, fungicides and algaecides. Pharmaceutically active ingredients include any compound that provides prophylactic and/or therapeutic properties when administered to, for example, humans. Examples include, but are not limited to, pharmaceutical actives, therapeutic actives, veterinarial actives, nutraceuticals, and growth regulators. Reference in this specification to a specific active ingredient is also to be understood to include the active ingredient in the form of acid addition salts, solvates, hydrates and the like (see pages 6-7). It is very clear that Lukas explicitly teach growth regulators as what Applicant claims. The examiner indeed acknowledged that Lukas and Ortyl et al. do not explicitly teach Methoprene. However, the deficiency is cured by the teachings of Miller et al.
Miller et al. teach compositions of insect regulators comprising monostearin, carnuba wax, barium sulfate, methoprene, and diflubenzuron are selectively formulated into a sustained-release bolus and orally administered to livestock to control the larvacidal activity of arthropods in the manure of the livestock (see abstract). A sustained release bolus formulation for the control of arthropods in cattle manure, said formulation comprising the following composition: about 4-17 parts monostearin, about 4-10 parts carnuba wax, about 70-75 parts Barium Sulfate, and about 1-15 parts Methoprene (claim 1). Repeated treatment of livestock is expensive in terms of both labor and insecticide. To compensate for rapid degradation of the pesticides on animals, the producer must apply larger quantities than are necessary for control of the immediate population if toxic levels are to be maintained for any length of time. Such a practice is wasteful of insecticide, results in greater contamination to the environment, and increases the probability of toxicity to animals and of residues in animal products. Therefore, one of the objectives of studies conducted at the U.S. Livestock Insects Laboratory, Kerrville, Tex., is to develop techniques that will make it possible to maintain the minimum effective level of toxicant on livestock over an extended period and thereby to increase the efficacy, efficiency, and safety of livestock pest control. This report deals with our efforts to use controlled-release technology against horn flies, Haematobia irritans (L.), common cattle grubs, Hypoderma lineatum (De Villers), and face fly, Musca autumnalis (DeGeer). Boluses have been used in veterinary medicine to provide nutritional and therapeutic substances to animals for predetermined periods. But, for several reasons the technique has not been used in the control of livestock pests: (1) the effective dose of most conventional insecticides is usually too large for the bolus form to be practical; (2) many insecticides are degraded by the digestive processes of the animal and by the environment; and (3) conventional insecticides can accumulate in animal tissues and thereby produce objectionable residues. However, insect growth regulators (IGR's) are chemicals of another type and might be more acceptable in a bolus than conventional insecticides. Insect growth regulators have been used successfully in the control of dung breeding pests of cattle for several years. Complete inhibition of development in manure has been achieved by administering insect growth regulators (IGR) to cattle in ground feed (Harris et al, 1973), in mineral blocks (Harris et al, 1974) and in drinking water (Beadles et al, 1975; Miller et al, 1976, 1977). Free-choice consumption and the resultant variations in dosage are inherent problems in the practical application of any of these techniques. Additionally, in some areas, animals will not consume supplemental minerals since their mineral requirements are amply met by the natural diet. The presence of untreatable sources of water (streams, rainfall) can interfere with the use of a water treatment. The use of sustained-release bolus formulations is another approach to supplying animals with small daily dosages of materials. Boluses have been used in animal husbandry to provide nutritional and therapeutic substances such as trace elements, antibiotics, anthelmintics, animal hormones, and growth stimulants over predetermined periods of time. The prior art for these dosages forms is adequately described in patent literature such as, for example, U.S. Pat. No. 3,056,724 (Marston 1962), U.S. Pat. No. 3,507,952 (Rednick and Tucker 1970) and U.S. Pat. No. 3,535,419 (Siegrist and Katz 1970). However, bolus dosage forms have not been used in the control of livestock arthropods because the effective dosage of most conventional insecticides is usually too large to make the bolus form practical, many insecticides are destroyed by digestive process and environment, and conventional insecticides are often accumulated in animal tissues and, thereby produce undesirable residues. The use of sustained-release bolus formulations to administer insect growth regulators for the control of livestock pests overcomes many of the aforementioned problems associated with ad lib treatments. Additionally, the efficacy and relative safety to insect growth regulators enables the use of the bolus treatment for long-lasting control measures (see entire column 1 and 2).
It would have been prima facie obvious to one of ordinary skill in the art at the time the claimed invention was made to modify the sustained (controlled) release dosage form of LUKAS and Ortyl et al. for the delivery of Methoprene because Miller et al. teach compositions of insect regulators comprising monostearin, carnuba wax, barium sulfate, methoprene, and diflubenzuron are selectively formulated into a sustained-release bolus and orally administered to livestock to control the larvacidal activity of arthropods in the manure of the livestock (see abstract). A sustained release bolus formulation for the control of arthropods in cattle manure, said formulation comprising the following composition: about 4-17 parts monostearin, about 4-10 parts carnuba wax, about 70-75 parts Barium Sulfate, and about 1-15 parts Methoprene (claim 1). One of ordinary skill in the art would have been motivated to do so because first LUKAS teach that its formulation is useful to deliver a compound having a beneficial effect when introduced into a system such as a biological system. For example, the active ingredient may be a biologically active compound for introduction into a human, animal, plant, water body or soil strata. Examples of biologically active compounds for this purpose include pharmaceutically active ingredients and agrochemicals. Exemplary agrochemicals include fertilisers, nutrients, pesticides, fungicides and algaecides. Pharmaceutically active ingredients include any compound that provides prophylactic and/or therapeutic properties when administered to, for example, humans. Examples include, but are not limited to, pharmaceutical actives, therapeutic actives, veterinarial actives, nutraceuticals, and growth regulators. Reference in this specification to a specific active ingredient is also to be understood to include the active ingredient in the form of acid addition salts, solvates, hydrates and the like (see pages 6-7). Furthermore, Miller et al. teach that repeated treatment of livestock is expensive in terms of both labor and insecticide. To compensate for rapid degradation of the pesticides on animals, the producer must apply larger quantities than are necessary for control of the immediate population if toxic levels are to be maintained for any length of time. Such a practice is wasteful of insecticide, results in greater contamination to the environment, and increases the probability of toxicity to animals and of residues in animal products. Therefore, one of the objectives of studies conducted at the U.S. Livestock Insects Laboratory, Kerrville, Tex., is to develop techniques that will make it possible to maintain the minimum effective level of toxicant on livestock over an extended period and thereby to increase the efficacy, efficiency, and safety of livestock pest control. This report deals with our efforts to use controlled-release technology against horn flies, Haematobia irritans (L.), common cattle grubs, Hypoderma lineatum (De Villers), and face fly, Musca autumnalis (DeGeer). Boluses have been used in veterinary medicine to provide nutritional and therapeutic substances to animals for predetermined periods. But, for several reasons the technique has not been used in the control of livestock pests: (1) the effective dose of most conventional insecticides is usually too large for the bolus form to be practical; (2) many insecticides are degraded by the digestive processes of the animal and by the environment; and (3) conventional insecticides can accumulate in animal tissues and thereby produce objectionable residues. However, insect growth regulators (IGR's) are chemicals of another type and might be more acceptable in a bolus than conventional insecticides. Insect growth regulators have been used successfully in the control of dung breeding pests of cattle for several years. Complete inhibition of development in manure has been achieved by administering insect growth regulators (IGR) to cattle in ground feed (Harris et al, 1973), in mineral blocks (Harris et al, 1974) and in drinking water (Beadles et al, 1975; Miller et al, 1976, 1977). Free-choice consumption and the resultant variations in dosage are inherent problems in the practical application of any of these techniques. Additionally, in some areas, animals will not consume supplemental minerals since their mineral requirements are amply met by the natural diet. The presence of untreatable sources of water (streams, rainfall) can interfere with the use of a water treatment. The use of sustained-release bolus formulations is another approach to supplying animals with small daily dosages of materials. Boluses have been used in animal husbandry to provide nutritional and therapeutic substances such as trace elements, antibiotics, anthelmintics, animal hormones, and growth stimulants over predetermined periods of time. The prior art for these dosages forms is adequately described in patent literature such as, for example, U.S. Pat. No. 3,056,724 (Marston 1962), U.S. Pat. No. 3,507,952 (Rednick and Tucker 1970) and U.S. Pat. No. 3,535,419 (Siegrist and Katz 1970). However, bolus dosage forms have not been used in the control of livestock arthropods because the effective dosage of most conventional insecticides is usually too large to make the bolus form practical, many insecticides are destroyed by digestive process and environment, and conventional insecticides are often accumulated in animal tissues and, thereby produce undesirable residues. The use of sustained-release bolus formulations to administer insect growth regulators for the control of livestock pests overcomes many of the aforementioned problems associated with ad lib treatments. Additionally, the efficacy and relative safety to insect growth regulators enables the use of the bolus treatment for long-lasting control measures (see entire column 1 and 2). Furthermore, in the case where the claimed ranges for amount of ingredients and active and also particle sizes “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). Additionally, differences in concentration 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). 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). The skilled artisan would have had a reasonable chance of expectation of success in combining the teachings of LUKAS, Ortyl et al., and Miller et al. because all of the references teach sustained or controlled release delivery of actives through solid dosage forms.
With regard to the limitation reciting “…, which duration is selected from the group consisting of 1, 2, or 3 days.”, it should be noticed that both LUKAS and Miller et al. are drawn to controlled or sustained release formulations. Furthermore, the combination teachings of LUKAS, Ortyl et al., and Miller et al. met the claimed composition. Hence, all pharmacokinetic or pharmacodynamic profiles Applicant recites would necessarily be there. “[I]nherency may supply a missing claim limitation in an obviousness analysis." PAR, 773 F.3d at 1194-1195 ; see also Endo Pharms. Sols., Inc. v. Custopharm Inc., 894 F.3d 1374 , 1381 , 127 U.S.P.Q.2D (BNA) 1409 (Fed. Cir. 2018) ("An inherent characteristic of a formulation can be part of the prior art in an obviousness analysis even if the inherent characteristic was unrecognized or unappreciated by a skilled artisan."). It is long settled that in the context of obviousness, the "mere recitation of a newly discovered function or property, inherently possessed by things in the prior art, does not distinguish a claim drawn to those things from the prior art." In re Oelrich, 666 F.2d 578 , 581 (C.C.P.A. 1981). The Supreme Court explained long ago that "[i]t is not invention to perceive that the product which others had discovered had qualities they failed to detect." Gen. Elec. Co. v. Jewel Incandescent Lamp Co., 326 U.S. 242 , 249 , 66 S. Ct. 81 , 90 L. Ed. 43 , 1946 Dec. Comm'r Pat. 611 (1945). We too have previously explained that "an obvious formulation cannot become nonobvious simply by administering it to a patient and claiming the resulting serum concentrations," because "[t]o hold otherwise would allow any formulation—no matter how obvious—to become patentable merely by testing and claiming an inherent property." Santarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344 , 1354 (Fed. Cir. 2012). In In re Kao, we found that the claimed controlled-release oxymorphone formulation was obvious because an inherent pharmacokinetic property of oxymorphone that was present in controlled-release oxymorphone "add[ed] nothing of patentable consequence." In re Huai-Hung Kao, 639 F.3d 1057 , 1070 , 98 U.S.P.Q.2D (BNA) 1799 (Fed. Cir. 2011). In In re Kubin, we found an inherent property obvious, explaining that "[e]ven if no prior art of record explicitly discusses the [limitation], the . . . application itself instructs that [the limitation] is not an additional requirement imposed by the claims on the [claimed protein], but rather a property necessarily present in [the claimed protein]." In re Kubin, 561 F.3d 1351 , 1357 , 90 U.S.P.Q.2D (BNA) 1417 (Fed. Cir. 2009). Our predecessor court similarly concluded that it "is not the law" that "a structure suggested by the prior art, and, hence, potentially in the possession of the public, is patentable . . . because it also possesses an [i]nherent, but hitherto unknown, function which [the patentees] claim to have discovered." In re [*1191] Wiseman, 596 F.2d 1019 , 1023 (C.C.P.A. 1979). Inherency, however, is a "high standard," that is "carefully circumscribed in the context of obviousness." PAR, 773 F.3d at 1195 . Inherency "may not be established by probabilities or possibilities," and "[t]he mere fact that a certain thing may result from a given set of circumstances is not sufficient." Oelrich, 666 F.2d at 581 (emphasis added) (quoting Hansgirg v. Kemmer, 102 F.2d 212 , 214 , 26 C.C.P.A. 937 , 1939 Dec. Comm'r Pat. 327 (C.C.P.A. 1939); see also In re Rijckaert, 9 F.3d 1531 , 1533-1534 (Fed. Cir. 1993). Rather, inherency renders a claimed limitation obvious only if the limitation is "necessarily present," or is "the natural result of the combination of elements explicitly disclosed by the prior art." PAR, 773 F.3d at 119511 -96; see also Alcon Research, Ltd. v. Apotex Inc., 687 F.3d 1362 , 1369 (Fed. Cir. 2012) (relying on inherency where the claims recited "a property that is necessarily present" in the prior art). "If . . . the disclosure is sufficient to show that the natural result flowing from the operation as taught would result in the performance of the questioned function, it seems to be well settled that the disclosure should be regarded as sufficient" to render the function inherent. Oelrich, 666 F.2d at 581 (quoting Hansgirg v. Kemmer, 102 F.2d 212 , 214 , 26 C.C.P.A. 937 , 1939 Dec. Comm'r Pat. 327 (C.C.P.A. 1939)). On appeal, Persion contends that the district court erred in applying the inherency doctrine in its obviousness analysis because Devane does not teach administering its hydrocodone-only formulation to patients with mild or moderate hepatic impairment. Thus, Persion asserts, "'the natural result flowing from the operation as taught' in Devane cannot be the claimed [pharmacokinetic] values for [hepatically impaired] patients." Appellant's Br. 37 (quoting Oelrich, 666 F.2d at 581 ); Reply Br. 19. To the extent Persion contends that inherency can only satisfy a claim limitation when all other limitations are taught in a single reference, that position is contrary to our prior recognition that "inherency may supply a missing claim limitation in an obviousness analysis" where the limitation at issue is "the natural result of the combination of prior art elements." PAR, 773 F.3d at 1194-1195 (emphasis added, internal quotations omitted). Here, the district court specifically found that Devane, together with Jain, the state of the prior art at the time of invention, and the Vicodin and Lortab labels, taught the combination of elements that inherently result in the claimed pharmacokinetic parameters. The district court found that a person of ordinary skill in the art would have been motivated, with reasonable expectation of success, to administer an unadjusted dose of the Devane formulation to hepatically impaired patients. There was also no dispute that the Devane formulation, which was identical to the Zohydro ER formulation described in the patents in suit, necessarily exhibited the claimed parameters under these conditions. Pernix, 323 F. Supp. 3d at 607 , 610 . In this context, the district court did not err by finding that the pharmacokinetic limitations of the asserted claims were inherent and added no patentable weight to the pharmacokinetic claims.
With regard to the preamble recitation “A feed-through sustained-release insecticide composition” it is an intended use limitation. 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 structure is capable of performing the intended use, then it meets the claim.
Applicant also further argues, the current claims recite a “spheronizing agent,” which refers to an agent that together with an active ingredient and a wax-like agent, forms a cohesive plastic mass that may be subsequently spheronized to produce spherical pellets or fragmented to form non-spherical pellets. (See, paragraph [0144] of US 2021/0113469). In contrast, the microcrystalline cellulose of Lukas is an anti-static agent. (Abstract). The anti-static agent is used as a “dusting” (See, p. 5, line 24; claim 8) of the core, and is certainly not an agent to form a cohesive plastic mass. The anti-static agent as taught in Lukas is about 0.5% w/w as disclosed on page 22, line 12; page 20, line 12, whereas claim 6 recites 5% to about 40% of the spheronizing agent. A much greater percent.
The above assertions are not found persuasive because Lukas clearly teach microcrystalline cellulose which is the same material as what Applicant uses as the spheronizing agent. "Products of identical chemical composition cannot 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. (Applicant argued that the claimed composition was a pressure sensitive adhesive containing a tacky polymer while the product of the reference was hard and abrasion resistant. "The Board correctly found that the virtual identity of monomers and procedures sufficed to support a prima facie case of unpatentability of Spada’s polymer latexes for lack of novelty."). It is immaterial whether one calls it spheronizing agent and another calls microcrystalline cellulose anti-static agent. Additionally, Ortyl et al. also teach microcrystalline cellulose.
Applicant further argues Ortyl et al. does not supply the deficiencies of the primary reference. Ortyl et al. teaches a pharmaceutical composition in solid unit dosage form, comprising, a) a therapeutically effective amount of a piperidinoalkanol compound or a pharmaceutically acceptable salt thereof, and, b) at least one inert ingredient (Abstract). Ortyl et al. do not teach an insect growth regulator, methoprene or even an insecticide. Methoprene is not a piperidineoalkanol. The structure of methoprene and the structure of piperdinoalkanols have nothing in common. A skilled person would not modify the teaching of Lukas to arrive at the present claims as there is no reasonable expectation of success. The rationale to support a conclusion that the claim would have been obvious is that “a person of ordinary skill in the art would have been motivated to combine the prior art to achieve the claimed invention and whether there would have been a reasonable expectation of success in doing so.” DyStar Textilfarben GmbH & Co. Deutschland KG y. C.H. Patrick Co., 464 F.3d 1356, 1360, 80 USPQ2d 1641, 1645 (Fed. Cir. 2006). MPEP § 2143.
The above assertions are not found persuasive because first of all Ortyl to be a proper reference to be combinable with LUKAS and Miller et al. do not necessarily have to teach Methoprene or insect growth regulator as those limitations are clearly covered by the teachings of LUKAS and Miller et al. as described above. Ortyl is incorporated in the rejections to render obvious why one of ordinary skill in the art would have been motivated to incorporate pregelatinized starch and its amounts and the amounts of microcrystalline cellulose. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Ortyl et al. teach a pharmaceutical composition in solid unit dosage form, comprising, a) a therapeutically effective amount of a piperidinoalkanol compound or a pharmaceutically acceptable salt thereof; and, b) at least one inert ingredient (see abstract). Efforts have focused on improving the bioavailability of various piperidinoalkanol compounds in order to improve their therapeutic efficiency. The present invention relates to pharmaceutical compositions and pharmaceutical compositions in solid unit dosage form wherein the piperidinoalkanol compound, or a pharmaceutically acceptable salt thereof, is in combination with inert ingredients (column 1, lines 45-52). As used herein the term "inert ingredient" refers to those therapeutically inert ingredients that are well known in the art of pharmaceutical science which can be used singly or in various combinations, and include, for example, binders, diluents, lubricants, glidants, sweetening agents, disintegrants, coloring agents, flavoring agents, antioxidants, solubilizing agents, coating agents and the like, as are disclosed in The United States Pharmacopeia, XXII, 1990, (1989 The United States Pharmacopeial Convention, Inc.), pages 1857-1859, which is incorporated herein by reference. For example, the following inert ingredients can be utilized singly or in various combinations; binders such as gelatin, polyvinylpyrrolidone (PVP), pregelatinized starch, povidone, cellulose derivatives including methyl cellulose, carboxymethyl cellulose, hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), sucrose and the like; diluents such as calcium carbonate, lactose, starch, microcrystalline cellulose, and the like; lubricants such as magnesium stearate, calcium stearate, zinc stearate, stearic acid, talc, hydrogenated vegetable oil and the like; glidants such as silicon dioxide, talc and the like; disintegrants such as alginic acid, methacrylic acid DVB, cross-linked PVP, microcrystalline cellulose, croscarmellose sodium, crospovidone, polacrilin potassium, sodium starch glycolate, starch, pregelatinized starch and the like; preferred disintegrants are croscarmellose sodium, starch, pregelatinized starch and sodium starch glycolate with croscarmellose sodium being the most preferred disintegrant; sweetening agents; coloring agents; flavoring agents; antioxidants; and the like. The above inert ingredients can be present in amounts up to about 95% of the total composition weight (column 13, lines 15-46).
A suitable combination of inert ingredients comprises microcrystalline cellulose, pregelatinized starch, gelatin, magnesium stearate, calcium carbonate and sodium starch glycolate, in amounts of from about 20% to about 85%, 5% to about 50%, 1% to about 15%, 0.05% to about 3%, 5% to about 50%, and 1% to about 15%. A preferred combination of inert ingredients is microcrystalline cellulose, pregelatinized starch, calcium carbonate, magnesium stearate and sodium starch glycolate in amounts of from about 20% to about 85%, 5% to about 50%, 5% to about 50%, 0.05% to about 3%, and 1% to about 15%. Another preferred combination of inert ingredients comprises: microcrystalline cellulose, pregelatinized starch, magnesium stearate, and croscarmellose sodium in amounts of from about, 20% to about 85%, 5% to about 50%, 0.05 to about 3%, 1% to about 10%. The most preferred combination of inert ingredients is croscarmellose sodium, microcrystalline cellulose, lactose, pregelatinized starch and gelatin, in amounts of from about 1% to about 10%, 20% to about 85%, 20% to about 85%, 1% to about 30% and 1% to about 15% respectively. The most especially preferred combination of inert ingredients is croscarmellose sodium, microcrystalline cellulose, lactose, pregelatinized starch, gelatin and magnesium stearate, in amounts of from about 1% to about 10%, 20% to about 85%, 20% to about 85%, 1% to about 30%, 1% to about 15% and 0.05% to about 3% respectively. The following entries 1 through 7 in Table 5, provide the most preferred amounts of the respective inert ingredients which can be utilized in preparation of the tablet or capsule dosage forms (column 13, lines 47-67 and column 14, lines 1-8).
It would have been prima facie obvious to one of ordinary skill in the art at the time the claimed invention was made to modify the teachings of LUKAS via incorporating pregelatinized starch and microcrystalline cellulose in amounts as recited because Ortyl et al. teach a pharmaceutical composition in solid unit dosage form, comprising, a) a therapeutically effective amount of a piperidinoalkanol compound or a pharmaceutically acceptable salt thereof; and, b) at least one inert ingredient (see abstract). Efforts have focused on improving the bioavailability of various piperidinoalkanol compounds in order to improve their therapeutic efficiency. The present invention relates to pharmaceutical compositions and pharmaceutical compositions in solid unit dosage form wherein the piperidinoalkanol compound, or a pharmaceutically acceptable salt thereof, is in combination with inert ingredients (column 1, lines 45-52). As used herein the term "inert ingredient" refers to those therapeutically inert ingredients that are well known in the art of pharmaceutical science which can be used singly or in various combinations, and include, for example, binders, diluents, lubricants, glidants, sweetening agents, disintegrants, coloring agents, flavoring agents, antioxidants, solubilizing agents, coating agents and the like, as are disclosed in The United States Pharmacopeia, XXII, 1990, (1989 The United States Pharmacopeial Convention, Inc.), pages 1857-1859, which is incorporated herein by reference. For example, the following inert ingredients can be utilized singly or in various combinations; binders such as gelatin, polyvinylpyrrolidone (PVP), pregelatinized starch, povidone, cellulose derivatives including methyl cellulose, carboxymethyl cellulose, hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), sucrose and the like; diluents such as calcium carbonate, lactose, starch, microcrystalline cellulose, and the like; lubricants such as magnesium stearate, calcium stearate, zinc stearate, stearic acid, talc, hydrogenated vegetable oil and the like; glidants such as silicon dioxide, talc and the like; disintegrants such as alginic acid, methacrylic acid DVB, cross-linked PVP, microcrystalline cellulose, croscarmellose sodium, crospovidone, polacrilin potassium, sodium starch glycolate, starch, pregelatinized starch and the like; preferred disintegrants are croscarmellose sodium, starch, pregelatinized starch and sodium starch glycolate with croscarmellose sodium being the most preferred disintegrant; sweetening agents; coloring agents; flavoring agents; antioxidants; and the like. The above inert ingredients can be present in amounts up to about 95% of the total composition weight (column 13, lines 15-46). One of ordinary skill in the art would have been motivated to do so because Ortyl et al. teach that a suitable combination of inert ingredients comprises microcrystalline cellulose, pregelatinized starch, gelatin, magnesium stearate, calcium carbonate and sodium starch glycolate, in amounts of from about 20% to about 85%, 5% to about 50%, 1% to about 15%, 0.05% to about 3%, 5% to about 50%, and 1% to about 15%. A preferred combination of inert ingredients is microcrystalline cellulose, pregelatinized starch, calcium carbonate, magnesium stearate and sodium starch glycolate in amounts of from about 20% to about 85%, 5% to about 50%, 5% to about 50%, 0.05% to about 3%, and 1% to about 15%. Another preferred combination of inert ingredients comprises: microcrystalline cellulose, pregelatinized starch, magnesium stearate, and croscarmellose sodium in amounts of from about, 20% to about 85%, 5% to about 50%, 0.05 to about 3%, 1% to about 10%. The most preferred combination of inert ingredients is croscarmellose sodium, microcrystalline cellulose, lactose, pregelatinized starch and gelatin, in amounts of from about 1% to about 10%, 20% to about 85%, 20% to about 85%, 1% to about 30% and 1% to about 15% respectively. The most especially preferred combination of inert ingredients is croscarmellose sodium, microcrystalline cellulose, lactose, pregelatinized starch, gelatin and magnesium stearate, in amounts of from about 1% to about 10%, 20% to about 85%, 20% to about 85%, 1% to about 30%, 1% to about 15% and 0.05% to about 3% respectively. The following entries 1 through 7 in Table 5, provide the most preferred amounts of the respective inert ingredients which can be utilized in preparation of the tablet or capsule dosage forms (column 13, lines 47-67 and column 14, lines 1-8). It should be noticed that these are conventionally known inert pharmaceutical ingredients that are useful to all classes of actives taught by LUKAS. 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. "Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." 325 U.S. at 335, 65 USPQ at 301.). Furthermore, in the case where the claimed ranges for amount of ingredients and active and also particle sizes “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). Additionally, differences in concentration 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). 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). The skilled artisan would have had a reasonable chance of expectation of success in combining the teachings of LUKAS and Ortyl et al. because both references teach sustained or controlled release delivery of actives through solid dosage forms.
Applicant further argues the mode of action of the present claims is different. In the feed through formulation as claimed, for example, cattle consume the feed, the IGR passes through their digestive system and into the manure. In this way, the IGR targets the manure directly, where flies lay their eggs, effectively disrupting the fly lifecycle.
The above assertions are not found persuasive because since the combination teachings of LUKAS, Ortyl, and Miller clearly met the claimed composition or product the mode of action would necessarily be the same, substantially similar, or will be there. Additionally, the examiner reminds Applicant that the claims are drawn to a composition not to a method of use following a specific mechanisms or steps.

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