DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Formal Matters
Applicant’s response in the reply filed on 01 April 2026 are acknowledged and have been fully considered. Claims 1-18 are pending. Claims 1-16 are under consideration in the instant office action. Claims 17-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 30 November 2023 are noted and the submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the examiner has considered the references. A signed copy is attached herein.
Election/Restrictions
Applicant's election with traverse of Group I (claims 1-16) in the reply filed on 01 April 2026 is acknowledged. Additionally, Applicant’s election with traverse of the species disintegrating promoting excipient premix comprising mannitol, xylitol, dibasic calcium phosphate anhydrous, crospovidone, and microcrystalline cellulose of claim 5 for further prosecution at this time in the reply filed on 01 April 2026 is also acknowledged.
The traversal is on the ground(s) that the basis for Applicant's traversal is that examination of groups II and III do not impose an undue burden on the Examiner. MPEP § 803 states that "[i]f the search and examination of an entire application can be made without serious burden, the examiner must examine it on the merits, even though it includes claims to independent or distinct inventions." Applicant submits that there is no undue burden in this case and therefore respectfully requests examination of all currently pending claims.
This is not found persuasive because the restriction requirement is based on the finding that Groups I-III lack unity of invention because even though the inventions of these groups require the technical feature of the tablet of claim 1, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Chen et al. (EP2480215). Regarding claim 1, Chen et al. teach in certain embodiments, the chewing includes at least two layers, e.g., with different types and/or concentrations of amorphous carbohydrate polymers and/or other ingredients or different concentrations of pharmaceutically active agents. Such an embodiment is shown in FIGS. 2A-2D. In one embodiment, the lozenge is a bilayer form; wherein the first layer is a lozenge form and the second layer is a orally disintegrating form. In one embodiment the first layer is a lozenge form and the second layer is a lozenge form. In one embodiment the lozenge form layer is free of a material that reacts to RF heating. In one embodiment, the lozenge form layer or the orally disintegrating form layer is first compressed as a layer, then the powder blend is added to the compressed lozenge or compressed orally disintegrating form layer and the entire form is energized utilizing the RF apparatus (paragraph 0093). In another embodiment, the lozenge product further includes a second layer which is not a lozenge layer (e.g., a layer having orally disintegrating properties). In such an embodiment, upon administration of such a lozenge product having an additional orally disintegrating layer, the orally disintegrating layer quickly disintegrates in the mouth of the user, leaving the lozenge product to be sucked on by the user. In one such embodiment, the orally disintegrating layer contains one pharmaceutically active agent (e.g., an analgesic, antihistamine, decongestant, cough suppressant, or expectorant) and the lozenge product either does not contain a pharmaceutically active agent or contains a different pharmaceutically active agent (e.g., menthol) (paragraph 0096). As discussed above, the lozenge shape is manufactured by forming a powder blend containing an amorphous carbohydrate polymer and optionally nicotine and/or other pharmaceutically active agent(s) and/or excipients. Examples of such excipients include, but are not limited to, glidants, lubricants, sweeteners, flavors and aromatics, enhancers, coloring agents, preservatives, vitamins, minerals, fluoride, and tooth whitening agents, and mixtures thereof. One or more of the above ingredients may be present on the same particle of the powder blend (paragraph 0010). Suitable lubricants include, but are not limited to, long chain fatty acids and their salts, such as magnesium stearate and stearic acid, talc, glycerides waxes, and mixtures thereof (paragraph 0011). Suitable glidants include, but are not limited to, colloidal silicon dioxide. Examples of sweeteners include, but are not limited to, synthetic or natural sugars; artificial sweeteners such as saccharin, sodium saccharin, aspartame, acesulfame, thaumatin, glycyrrhizin, sucralose, dihydrochalcone, alitame, miraculin, monellin, and stevside; sugar alcohols such as sorbitol, mannitol, glycerol, lactitol, maltitol, and xylitol; sugars extracted from sugar cane and sugar beet (sucrose), dextrose (also called glucose), fructose (also called laevulose), and lactose (also called milk sugar); isomalt, salts thereof, and mixtures thereof. Examples of flavors and aromatics include, but are not limited to, essential oils including distillations, solvent extractions, or cold expressions of chopped flowers, leaves, peel or pulped whole fruit comprising mixtures of alcohols, esters, aldehydes and lactones; essences including either diluted solutions of essential oils, or mixtures of synthetic chemicals blended to match the natural flavor of the fruit (e.g., strawberry, raspberry and black currant); artificial and natural flavors of brews and liquors, e.g., cognac, whisky, rum, gin, sherry, port, and wine; tobacco, coffee, tea, cocoa, and mint; fruit juices including expelled juice from washed, scrubbed fruits such as lemon, orange, and lime; spear mint, peppermint, wintergreen, cinnamon, cacoe/cocoa, vanilla, liquorice, menthol, eucalyptus, aniseeds nuts (e.g., peanuts, coconuts, hazelnuts, chestnuts, walnuts, colanuts), almonds, raisins; and powder, flour, or vegetable material parts including tobacco plant parts, e.g., genus Nicotiana, in amounts not contributing significantly to the level of nicotine, and ginger (paragraphs 0012-0014). In one embodiment, the amount of amorphous carbohydrate polymer in the powder blend/lozenge shape/lozenge product is from about 50 percent to about 99.9 percent, by weight, such as from about 80 percent to about 95 percent by weight (paragraph 0017). In one embodiment, the powder blend/lozenge shape/lozenge product contains a smoking cessation compound(s) such as: nicotine and/or metabolites thereof, such as cotinine, etc., (paragraph 0019). In one embodiment, lozenge product includes the nicotine compound in an amount of from about 0.05 to about 12 mg calculated as the free base form of nicotine per lozenge product, such as from about 0.2-6 mg, such as from about 0.5-5 mg. This may in different embodiments include 0.05, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 6, 7, 8, 9, 10, or 12 mg calculated as the free base form of nicotine per lozenge product (paragraph 0024). In one embodiment, the lozenge/powder blend/coating contains both nicotine and a buffering agent. In one embodiment, the lozenge is buffered such that upon administration of the lozenge, the pH of the saliva is transiently increased from about 0.2 to about 4 pH units, preferably from about 0.4 to about 2 pH units. The buffering is designed so as to achieve a transient buffering of the saliva of a subject during use of the lozenge product. As the change is transient, the pH will return to its normal value after a certain period of time (paragraph 0025). Examples of buffering agents include, but are not limited to, carbonates including carbonate, bicarbonate or sesquicarbonate, glycinate, phosphate, glycerophosphate or citrate of an alkali metal, such as potassium or sodium, or ammonium such as trisodium or tripotassium citrate, trisodium phosphate, disodium hydrogen phosphate, tripotassium phosphate, dipotassium hydrogen phosphate, calcium hydroxide, sodium glycinate, and trometamol (TRIS). Alkali metal carbonates, glycinates and phosphates are preferred buffering agents (paragraph 0026). The pharmaceutically active agent may be present in various forms. For example, the pharmaceutically active agent may be dispersed at the molecular level, e.g. melted, within the lozenge product, or may be in the form of particles, which in turn may be coated or uncoated. If the pharmaceutically active agent is in form of particles, the particles (whether coated or uncoated) typically have an average particle size of from about 1 to about 2000 microns. In one embodiment, such particles are crystals having an average particle size of from about 1 to about 300 microns. In another embodiment, the particles are granules or pellets having an average particle size of from about 50 to about 2000 microns, such as from about 50 to about 1000 microns, such as from about 100 to about 800 microns (paragraph 0047). The pharmaceutically active agent may be present in pure crystal form or in a granulated form prior to the addition of the taste masking coating. Granulation techniques may be used to improve the flow characteristics or particle size of the pharmaceutically active agents to make it more suitable for compaction or subsequent coating. Suitable binders for making the granulation include but are not limited to starch, polyvinylpyrrolidone, polymethacrylates, hydroxypropylmethylcellulose (which is Hypromellose), and hydroxypropylcellulose. The particles including pharmaceutically active agent(s) may be made by cogranulating the pharmaceutically active agent(s) with suitable substrate particles via any of the granulation methods known in the art. Examples of such granulation method include, but are not limited to, high sheer wet granulation and fluid bed granulation such as rotary fluid bed granulation (paragraph 0048). In one embodiment, a lubricant is added to forming cavity prior to the addition of the flowable powder blend. This lubricant may be a liquid or solid. Suitable lubricants include but are not limited to solid lubricants such as magnesium stearate, starch, calcium stearate, aluminum stearate and stearic acid; or liquid lubricants such as but not limited to simethicone, lecithin, vegetable oil, olive oil, or mineral oil. In certain embodiments, the lubricant is added at a percentage by weight of the lozenge of less than 5 percent, e.g. less than 2 percent, e.g. less than 0.5 percent (paragraph 0076). In one embodiment, the nicotine compound and/or the pharmaceutically active agent is in the form of a gel bead, which is liquid filled or semi-solid filled. The gel bead(s) are added as a portion of the powder blend. In one embodiment, the lozenge product of this invention has the added advantage of not requiring a strong compaction step, allowing for the use of liquid or semisolid filled particles or beads which are deformable since they will not rupture following the reduced pressure compaction step. These bead walls may contain gelling substances such as: gelatin; gellan gum; xanthan gum; agar; locust bean gum; carrageenan; polymers or polysaccharides such as but not limited to sodium alginate, calcium alginate, hypromellose, hydroxypropyl cellulose and pullulan; polyethylene oxide; and starches. The bead walls may further contain a plasticizer such as glycerin, polyethylene glycol, propylene glycol, triacetin, triethyl citrate and tributyl citrate. The pharmaceutically active agent may be dissolved, suspended or dispersed in a filler material such as but not limited to high fructose com syrup, sugars, glycerin, polyethylene glycol, propylene glycol, or oils such as but not limited to vegetable oil, olive oil, or mineral oil (paragraph 0091). Different bilayer tablet examples containing disintegrating layer and lozenge layer in mgs are taught in the examples.
Applicant also argues the claim requires all components (i)-(v), and the Office has made no showing that they are mutually exclusive species. Stated differently, components (i), (ii), (iii), (iv), and (v) are not alternatives of each other. Instead they are necessary components to the claimed tablet. Here, none of the dependent claims 2-7 and 10, as indicated by the Office, recite mutually exclusive characteristics of species of the claimed tablet. Instead, each dependent claim merely narrows a single, required component of the tablet of claim 1. Claims 2-4 progressively narrow the sensory marker/signal; claim 5 specifies the disintegration promoting excipient premix; claim 6 specifies the buffer system and hydrophilic matrix; claim 7 adds a lubricant; and claim 10 specifies the nicotine active agent. These claims are all drawn to the same tablet and different features; the claims are not directed to different species of tablet. Furthermore, the requirement for six simultaneous elections within a single claimed product improperly dismantles the claim into its constituent parts and treats each as an independent invention.
Applicant misunderstood the election of species requirement set forth in the previous office action. The examiner was requesting Applicant to elect species for each of the components: a specific species of a sensory marker/signal ingredient (claims 2-4 recite the species); a specific disintegration promoting excipient (claim 5 recites the species); a specific buffer system (claim 6 recites the species); a specific hydrophilic matrix (claim 6 recites the species); a specific lubricant (claim 7 recites the species); and a specific nicotine agent (claim 10 recites the species). The examiner was not asking Applicant to elect one from the above components. Upon further consideration by the examiner the species election requirement is hereby withdrawn and the claims are examined along with their generic recitations. However, the examiner maintains the Group election requirements as set forth above.
The requirement is still deemed proper and is therefore made FINAL.
Claim Objections
Claims 2-16 are objected to because of the following informalities: Independent claims start recitations with the article “A” or “An” and dependent claims start recitation with the proposition “The”. Dependent claims 2-16 start recitation with the article “A” contrary to the conventional claim construction language. Appropriate correction is required.
Claims 2-16 are objected to because of the following informalities: For purposes of clarity and readability in claims 2-12 and 15-16, Applicant should amend the claims to include a comma before the term “wherein”. In claims 13-14 Applicant should include a comma before the term “comprising”. Appropriate correction is required.
Claim 5 is objected to because of the following informalities: Claim 5 should be reformatted to recite “The tablet according to claim 1, wherein the disintegration promoting excipient of (a) comprises a disintegration promoting excipient premix comprising mannitol, xylitol, dibasic calcium phosphate anhydrous, crospovidone, and microcrystalline cellulose.”. Appropriate correction is required.
Claims 6 and 11-14 are objected to because of the following informalities: The terms “Hyperomellose”, the phrases “Nicotine Polacrilex”, and “Reference Product”, respectively are capitalized in the middle of sentences. Appropriate correction is required.
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 11-14 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.
Claims 11-12 which depend from claim 6 recite the limitation “the Nicotine Polacrilex” in claim 6. There is insufficient antecedent basis for this limitation in the claim.
Claims 13-14 which depend from claim 1 recite the limitation “the corresponding 2 mg or 4 mg Reference Product”. There is insufficient antecedent basis for this limitation in the claim.
In claim 13 the phrase “(calculated as nicotinee) is unclear. “Nicotinee” appears to be a typographical error (presumably intended as “nicotine”), but as written it renders the claim unclear. Additionally, in claim 13, it remains unclear whether the claim requires the tablet to contain exactly 2 mg or 4 mg of nicotine (calculated as free base or salt), or merely an amount that is nominally labeled as such.
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.
Claim(s) 1-4, 8-9, and 13-16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen Jen Chi et al. (EP2480215, previously provided to Applicant).
Chen Jen Chi et al. disclose in certain embodiments, the chewing includes at least two layers, e.g., with different types and/or concentrations of amorphous carbohydrate polymers and/or other ingredients or different concentrations of pharmaceutically active agents. Such an embodiment is shown in FIGS. 2A-2D. In one embodiment, the lozenge is a bilayer form; wherein the first layer is a lozenge form and the second layer is a orally disintegrating form. In one embodiment the first layer is a lozenge form and the second layer is a lozenge form. In one embodiment the lozenge form layer is free of a material that reacts to RF heating. In one embodiment, the lozenge form layer or the orally disintegrating form layer is first compressed as a layer, then the powder blend is added to the compressed lozenge or compressed orally disintegrating form layer and the entire form is energized utilizing the RF apparatus (paragraph 0093). In another embodiment, the lozenge product further includes a second layer which is not a lozenge layer (e.g., a layer having orally disintegrating properties). In such an embodiment, upon administration of such a lozenge product having an additional orally disintegrating layer, the orally disintegrating layer quickly disintegrates in the mouth of the user, leaving the lozenge product to be sucked on by the user. In one such embodiment, the orally disintegrating layer contains one pharmaceutically active agent (e.g., an analgesic, antihistamine, decongestant, cough suppressant, or expectorant) and the lozenge product either does not contain a pharmaceutically active agent or contains a different pharmaceutically active agent (e.g., menthol) (paragraph 0096). As discussed above, the lozenge shape is manufactured by forming a powder blend containing an amorphous carbohydrate polymer and optionally nicotine and/or other pharmaceutically active agent(s) and/or excipients. Examples of such excipients include, but are not limited to, glidants, lubricants, sweeteners, flavors and aromatics, enhancers, coloring agents, preservatives, vitamins, minerals, fluoride, and tooth whitening agents, and mixtures thereof. One or more of the above ingredients may be present on the same particle of the powder blend (paragraph 0010). Suitable lubricants include, but are not limited to, long chain fatty acids and their salts, such as magnesium stearate and stearic acid, talc, glycerides waxes, and mixtures thereof (paragraph 0011). Suitable glidants include, but are not limited to, colloidal silicon dioxide. Examples of sweeteners include, but are not limited to, synthetic or natural sugars; artificial sweeteners such as saccharin, sodium saccharin, aspartame, acesulfame, thaumatin, glycyrrhizin, sucralose, dihydrochalcone, alitame, miraculin, monellin, and stevside; sugar alcohols such as sorbitol, mannitol, glycerol, lactitol, maltitol, and xylitol; sugars extracted from sugar cane and sugar beet (sucrose), dextrose (also called glucose), fructose (also called laevulose), and lactose (also called milk sugar); isomalt, salts thereof, and mixtures thereof. Examples of flavors and aromatics include, but are not limited to, essential oils including distillations, solvent extractions, or cold expressions of chopped flowers, leaves, peel or pulped whole fruit comprising mixtures of alcohols, esters, aldehydes and lactones; essences including either diluted solutions of essential oils, or mixtures of synthetic chemicals blended to match the natural flavor of the fruit (e.g., strawberry, raspberry and black currant); artificial and natural flavors of brews and liquors, e.g., cognac, whisky, rum, gin, sherry, port, and wine; tobacco, coffee, tea, cocoa, and mint; fruit juices including expelled juice from washed, scrubbed fruits such as lemon, orange, and lime; spear mint, peppermint, wintergreen, cinnamon, cacoe/cocoa, vanilla, liquorice, menthol, eucalyptus, aniseeds nuts (e.g., peanuts, coconuts, hazelnuts, chestnuts, walnuts, colanuts), almonds, raisins; and powder, flour, or vegetable material parts including tobacco plant parts, e.g., genus Nicotiana, in amounts not contributing significantly to the level of nicotine, and ginger (paragraphs 0012-0014). In one embodiment, the amount of amorphous carbohydrate polymer in the powder blend/lozenge shape/lozenge product is from about 50 percent to about 99.9 percent, by weight, such as from about 80 percent to about 95 percent by weight (paragraph 0017). In one embodiment, the powder blend/lozenge shape/lozenge product contains a smoking cessation compound(s) such as: nicotine and/or metabolites thereof, such as cotinine, etc., (paragraph 0019). In one embodiment, lozenge product includes the nicotine compound in an amount of from about 0.05 to about 12 mg calculated as the free base form of nicotine per lozenge product, such as from about 0.2-6 mg, such as from about 0.5-5 mg. This may in different embodiments include 0.05, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 6, 7, 8, 9, 10, or 12 mg calculated as the free base form of nicotine per lozenge product (paragraph 0024). In one embodiment, the lozenge/powder blend/coating contains both nicotine and a buffering agent. In one embodiment, the lozenge is buffered such that upon administration of the lozenge, the pH of the saliva is transiently increased from about 0.2 to about 4 pH units, preferably from about 0.4 to about 2 pH units. The buffering is designed so as to achieve a transient buffering of the saliva of a subject during use of the lozenge product. As the change is transient, the pH will return to its normal value after a certain period of time (paragraph 0025). Examples of buffering agents include, but are not limited to, carbonates including carbonate, bicarbonate or sesquicarbonate, glycinate, phosphate, glycerophosphate or citrate of an alkali metal, such as potassium or sodium, or ammonium such as trisodium or tripotassium citrate, trisodium phosphate, disodium hydrogen phosphate, tripotassium phosphate, dipotassium hydrogen phosphate, calcium hydroxide, sodium glycinate, and trometamol (TRIS). Alkali metal carbonates, glycinates and phosphates are preferred buffering agents (paragraph 0026). The pharmaceutically active agent may be present in various forms. For example, the pharmaceutically active agent may be dispersed at the molecular level, e.g. melted, within the lozenge product, or may be in the form of particles, which in turn may be coated or uncoated. If the pharmaceutically active agent is in form of particles, the particles (whether coated or uncoated) typically have an average particle size of from about 1 to about 2000 microns. In one embodiment, such particles are crystals having an average particle size of from about 1 to about 300 microns. In another embodiment, the particles are granules or pellets having an average particle size of from about 50 to about 2000 microns, such as from about 50 to about 1000 microns, such as from about 100 to about 800 microns (paragraph 0047). The pharmaceutically active agent may be present in pure crystal form or in a granulated form prior to the addition of the taste masking coating. Granulation techniques may be used to improve the flow characteristics or particle size of the pharmaceutically active agents to make it more suitable for compaction or subsequent coating. Suitable binders for making the granulation include but are not limited to starch, polyvinylpyrrolidone, polymethacrylates, hydroxypropylmethylcellulose (which is Hypromellose), and hydroxypropylcellulose. The particles including pharmaceutically active agent(s) may be made by cogranulating the pharmaceutically active agent(s) with suitable substrate particles via any of the granulation methods known in the art. Examples of such granulation method include, but are not limited to, high sheer wet granulation and fluid bed granulation such as rotary fluid bed granulation (paragraph 0048). In one embodiment, a lubricant is added to forming cavity prior to the addition of the flowable powder blend. This lubricant may be a liquid or solid. Suitable lubricants include but are not limited to solid lubricants such as magnesium stearate, starch, calcium stearate, aluminum stearate and stearic acid; or liquid lubricants such as but not limited to simethicone, lecithin, vegetable oil, olive oil, or mineral oil. In certain embodiments, the lubricant is added at a percentage by weight of the lozenge of less than 5 percent, e.g. less than 2 percent, e.g. less than 0.5 percent (paragraph 0076). In one embodiment, the nicotine compound and/or the pharmaceutically active agent is in the form of a gel bead, which is liquid filled or semi-solid filled. The gel bead(s) are added as a portion of the powder blend. In one embodiment, the lozenge product of this invention has the added advantage of not requiring a strong compaction step, allowing for the use of liquid or semisolid filled particles or beads which are deformable since they will not rupture following the reduced pressure compaction step. These bead walls may contain gelling substances such as: gelatin; gellan gum; xanthan gum; agar; locust bean gum; carrageenan; polymers or polysaccharides such as but not limited to sodium alginate, calcium alginate, hypromellose, hydroxypropyl cellulose and pullulan; polyethylene oxide; and starches. The bead walls may further contain a plasticizer such as glycerin, polyethylene glycol, propylene glycol, triacetin, triethyl citrate and tributyl citrate. The pharmaceutically active agent may be dissolved, suspended or dispersed in a filler material such as but not limited to high fructose com syrup, sugars, glycerin, polyethylene glycol, propylene glycol, or oils such as but not limited to vegetable oil, olive oil, or mineral oil (paragraph 0091). Different bilayer tablet examples containing disintegrating layer and lozenge layer in mgs are taught in the examples.
With regard to the disintegrating time of (a) and (b) as recited in claims 8-9 respectively, Chen Jen Chi et al. teach that in another embodiment, the lozenge product further includes a second layer which is not a lozenge layer (e.g., a layer having orally disintegrating properties). In such an embodiment, upon administration of such a lozenge product having an additional orally disintegrating layer, the orally disintegrating layer quickly disintegrates in the mouth of the user, leaving the lozenge product to be sucked on by the user. It should be noticed that Chen Jen Chi et al. disclose identical structure as recited in claim 1. Therefore, the disintegrating property of each layer would be an innate property of the structure. he examiner reminds Applicant that 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). "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 or substantially similar structure, the properties applicant discloses and/or claims are necessarily present.
With regard to the pharmacokinetic parameter recitations of claims 13-14 the examiner reminds Applicant that Chen Jen Chi et al. clearly met the claimed structure of claim 1 which claims 13-14 depend from. The examiner reminds Applicant that 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). "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 or substantially similar structure, the properties applicant discloses and/or claims are necessarily present.
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 1-5, 8-9, and 13-16 are rejected under 35 U.S.C. 103 as being unpatentable over Chen Jen Chi et al. (EP2480215, previously provided to Applicant) in view of Al Husban et al. (US2019/0117577).
Applicants’ claims
Applicant claims a tablet for intra-oral delivery of nicotine. Dependent claims thereof recite additional features.
Determination of the Scope and Content of the Prior Art
(MPEP 2141.01)
Chen Jen Chi et al. teach in certain embodiments, the chewing includes at least two layers, e.g., with different types and/or concentrations of amorphous carbohydrate polymers and/or other ingredients or different concentrations of pharmaceutically active agents. Such an embodiment is shown in FIGS. 2A-2D. In one embodiment, the lozenge is a bilayer form; wherein the first layer is a lozenge form and the second layer is a orally disintegrating form. In one embodiment the first layer is a lozenge form and the second layer is a lozenge form. In one embodiment the lozenge form layer is free of a material that reacts to RF heating. In one embodiment, the lozenge form layer or the orally disintegrating form layer is first compressed as a layer, then the powder blend is added to the compressed lozenge or compressed orally disintegrating form layer and the entire form is energized utilizing the RF apparatus (paragraph 0093). In another embodiment, the lozenge product further includes a second layer which is not a lozenge layer (e.g., a layer having orally disintegrating properties). In such an embodiment, upon administration of such a lozenge product having an additional orally disintegrating layer, the orally disintegrating layer quickly disintegrates in the mouth of the user, leaving the lozenge product to be sucked on by the user. In one such embodiment, the orally disintegrating layer contains one pharmaceutically active agent (e.g., an analgesic, antihistamine, decongestant, cough suppressant, or expectorant) and the lozenge product either does not contain a pharmaceutically active agent or contains a different pharmaceutically active agent (e.g., menthol) (paragraph 0096). As discussed above, the lozenge shape is manufactured by forming a powder blend containing an amorphous carbohydrate polymer and optionally nicotine and/or other pharmaceutically active agent(s) and/or excipients. Examples of such excipients include, but are not limited to, glidants, lubricants, sweeteners, flavors and aromatics, enhancers, coloring agents, preservatives, vitamins, minerals, fluoride, and tooth whitening agents, and mixtures thereof. One or more of the above ingredients may be present on the same particle of the powder blend (paragraph 0010). Suitable lubricants include, but are not limited to, long chain fatty acids and their salts, such as magnesium stearate and stearic acid, talc, glycerides waxes, and mixtures thereof (paragraph 0011). Suitable glidants include, but are not limited to, colloidal silicon dioxide. Examples of sweeteners include, but are not limited to, synthetic or natural sugars; artificial sweeteners such as saccharin, sodium saccharin, aspartame, acesulfame, thaumatin, glycyrrhizin, sucralose, dihydrochalcone, alitame, miraculin, monellin, and stevside; sugar alcohols such as sorbitol, mannitol, glycerol, lactitol, maltitol, and xylitol; sugars extracted from sugar cane and sugar beet (sucrose), dextrose (also called glucose), fructose (also called laevulose), and lactose (also called milk sugar); isomalt, salts thereof, and mixtures thereof. Examples of flavors and aromatics include, but are not limited to, essential oils including distillations, solvent extractions, or cold expressions of chopped flowers, leaves, peel or pulped whole fruit comprising mixtures of alcohols, esters, aldehydes and lactones; essences including either diluted solutions of essential oils, or mixtures of synthetic chemicals blended to match the natural flavor of the fruit (e.g., strawberry, raspberry and black currant); artificial and natural flavors of brews and liquors, e.g., cognac, whisky, rum, gin, sherry, port, and wine; tobacco, coffee, tea, cocoa, and mint; fruit juices including expelled juice from washed, scrubbed fruits such as lemon, orange, and lime; spear mint, peppermint, wintergreen, cinnamon, cacoe/cocoa, vanilla, liquorice, menthol, eucalyptus, aniseeds nuts (e.g., peanuts, coconuts, hazelnuts, chestnuts, walnuts, colanuts), almonds, raisins; and powder, flour, or vegetable material parts including tobacco plant parts, e.g., genus Nicotiana, in amounts not contributing significantly to the level of nicotine, and ginger (paragraphs 0012-0014). In one embodiment, the amount of amorphous carbohydrate polymer in the powder blend/lozenge shape/lozenge product is from about 50 percent to about 99.9 percent, by weight, such as from about 80 percent to about 95 percent by weight (paragraph 0017). In one embodiment, the powder blend/lozenge shape/lozenge product contains a smoking cessation compound(s) such as: nicotine and/or metabolites thereof, such as cotinine, etc., (paragraph 0019). In one embodiment, lozenge product includes the nicotine compound in an amount of from about 0.05 to about 12 mg calculated as the free base form of nicotine per lozenge product, such as from about 0.2-6 mg, such as from about 0.5-5 mg. This may in different embodiments include 0.05, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 6, 7, 8, 9, 10, or 12 mg calculated as the free base form of nicotine per lozenge product (paragraph 0024). In one embodiment, the lozenge/powder blend/coating contains both nicotine and a buffering agent. In one embodiment, the lozenge is buffered such that upon administration of the lozenge, the pH of the saliva is transiently increased from about 0.2 to about 4 pH units, preferably from about 0.4 to about 2 pH units. The buffering is designed so as to achieve a transient buffering of the saliva of a subject during use of the lozenge product. As the change is transient, the pH will return to its normal value after a certain period of time (paragraph 0025). Examples of buffering agents include, but are not limited to, carbonates including carbonate, bicarbonate or sesquicarbonate, glycinate, phosphate, glycerophosphate or citrate of an alkali metal, such as potassium or sodium, or ammonium such as trisodium or tripotassium citrate, trisodium phosphate, disodium hydrogen phosphate, tripotassium phosphate, dipotassium hydrogen phosphate, calcium hydroxide, sodium glycinate, and trometamol (TRIS). Alkali metal carbonates, glycinates and phosphates are preferred buffering agents (paragraph 0026). The pharmaceutically active agent may be present in various forms. For example, the pharmaceutically active agent may be dispersed at the molecular level, e.g. melted, within the lozenge product, or may be in the form of particles, which in turn may be coated or uncoated. If the pharmaceutically active agent is in form of particles, the particles (whether coated or uncoated) typically have an average particle size of from about 1 to about 2000 microns. In one embodiment, such particles are crystals having an average particle size of from about 1 to about 300 microns. In another embodiment, the particles are granules or pellets having an average particle size of from about 50 to about 2000 microns, such as from about 50 to about 1000 microns, such as from about 100 to about 800 microns (paragraph 0047). The pharmaceutically active agent may be present in pure crystal form or in a granulated form prior to the addition of the taste masking coating. Granulation techniques may be used to improve the flow characteristics or particle size of the pharmaceutically active agents to make it more suitable for compaction or subsequent coating. Suitable binders for making the granulation include but are not limited to starch, polyvinylpyrrolidone, polymethacrylates, hydroxypropylmethylcellulose (which is Hypromellose), and hydroxypropylcellulose. The particles including pharmaceutically active agent(s) may be made by cogranulating the pharmaceutically active agent(s) with suitable substrate particles via any of the granulation methods known in the art. Examples of such granulation method include, but are not limited to, high sheer wet granulation and fluid bed granulation such as rotary fluid bed granulation (paragraph 0048). In one embodiment, a lubricant is added to forming cavity prior to the addition of the flowable powder blend. This lubricant may be a liquid or solid. Suitable lubricants include but are not limited to solid lubricants such as magnesium stearate, starch, calcium stearate, aluminum stearate and stearic acid; or liquid lubricants such as but not limited to simethicone, lecithin, vegetable oil, olive oil, or mineral oil. In certain embodiments, the lubricant is added at a percentage by weight of the lozenge of less than 5 percent, e.g. less than 2 percent, e.g. less than 0.5 percent (paragraph 0076). In one embodiment, the nicotine compound and/or the pharmaceutically active agent is in the form of a gel bead, which is liquid filled or semi-solid filled. The gel bead(s) are added as a portion of the powder blend. In one embodiment, the lozenge product of this invention has the added advantage of not requiring a strong compaction step, allowing for the use of liquid or semisolid filled particles or beads which are deformable since they will not rupture following the reduced pressure compaction step. These bead walls may contain gelling substances such as: gelatin; gellan gum; xanthan gum; agar; locust bean gum; carrageenan; polymers or polysaccharides such as but not limited to sodium alginate, calcium alginate, hypromellose, hydroxypropyl cellulose and pullulan; polyethylene oxide; and starches. The bead walls may further contain a plasticizer such as glycerin, polyethylene glycol, propylene glycol, triacetin, triethyl citrate and tributyl citrate. The pharmaceutically active agent may be dissolved, suspended or dispersed in a filler material such as but not limited to high fructose com syrup, sugars, glycerin, polyethylene glycol, propylene glycol, or oils such as but not limited to vegetable oil, olive oil, or mineral oil (paragraph 0091). Different bilayer tablet examples containing disintegrating layer and lozenge layer in mgs are taught in the examples.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP 2141.02)
Chen Jen Chi et al. do not specifically teach the disintegration promoting excipient premix as recited in claim 5. This deficiency is cured by the teachings of Al Husban et al.
Al Husban et al. teach rapidly disintegrating oral dosage forms, more particularly to rapidly disintegrating tablets containing (1S ,2S ,3R,5S)-3-[7-{[1R,2S)-2-(3,4-difluorophenyl)cyclopropyl]amino}-5-(propylthio)-3H-[1,2,3]-triazolo[4,5-d]pyrimidin-3-yl]-55-(2-hydroxyethoxy)cyclopentane-1,2-diol and a disintegrating excipient, wherein the tablet has a hardness of from about 50 to about 150N and a disintegration time of less than about 3 minutes (see claim 1). The tablet according to claim 1, wherein the at least one disintegrating excipient comprises a fast oral disintegrating excipient (claim 3). The tablet according to claim 1, wherein the at least one disintegrating excipient comprises at least one carbohydrate filler and at least one disintegrant (claim 4). The tablet according to claim 1, wherein the at least one disintegrating excipient comprises mannitol, xylitol, anhydrous dibasic calcium phosphate, crospovidone and microcrystalline cellulose (claim 7). The tablet according to claim 1, wherein the at least one disintegrating excipient is a disintegrating excipient pre-mix that is present in an amount ranging from about 50% to about 80% by weight of the tablet (claim 8). F-melt type C is the most preferred disintegrating excipient for use in the tablets of the invention. Thus, in one embodiment the at least one disintegrating excipient is a disintegrating excipient pre-mix comprising mannitol, xylitol, anhydrous dibasic calcium phosphate, crospovidone and microcrystalline cellulose. In a further embodiment, the at least one disintegrating excipient pre-mix comprises F-melt type C (paragraph 0027). The tablets of the invention should contain a sufficient amount of the at least one disintegrating excipient in order for the tablet to disintegrate within a sufficiently short time. However, the amount of the at least one disintegrating excipient must not be so high as to cause difficulties in the manufacture of the tablet in view of the adhesiveness and/or cohesiveness of ticagrelor. It has been surprisingly found that tablets of the invention in which the at least one disintegrating excipient is a disintegrating excipient pre-mix that is present in an amount ranging from about 50% to about 80% by weight of the tablet have an acceptable disintegration time (e.g. less than 3 minutes) while simultaneously allowing the adhesiveness and/or cohesiveness of ticagrelor to be adequately countered during the manufacture of the tablets. Thus, in a further embodiment, the at least one disintegrating excipient is a disintegrating excipient pre-mix present in an amount ranging from about 50% to about 80% by weight of the tablet (paragraph 0028).
Finding of Prima Facie Obviousness Rational and Motivation
(MPEP 2142-2143)
It would have been prima facie obvious to a person of ordinary skill in the before the effective filing date of the instant invention to modify the teachings of Chen Jen Chi et al. by utilizing the disintegrating agent pre-mix as recited in claim 5 because Al Husban et al. teach rapidly disintegrating oral dosage forms, more particularly to rapidly disintegrating tablets containing (1S ,2S ,3R,5S)-3-[7-{[1R,2S)-2-(3,4-difluorophenyl)cyclopropyl]amino}-5-(propylthio)-3H-[1,2,3]-triazolo[4,5-d]pyrimidin-3-yl]-55-(2-hydroxyethoxy)cyclopentane-1,2-diol and a disintegrating excipient, wherein the tablet has a hardness of from about 50 to about 150N and a disintegration time of less than about 3 minutes (see claim 1). The tablet according to claim 1, wherein the at least one disintegrating excipient comprises a fast oral disintegrating excipient (claim 3). The tablet according to claim 1, wherein the at least one disintegrating excipient comprises at least one carbohydrate filler and at least one disintegrant (claim 4). The tablet according to claim 1, wherein the at least one disintegrating excipient comprises mannitol, xylitol, anhydrous dibasic calcium phosphate, crospovidone and microcrystalline cellulose (claim 7). The tablet according to claim 1, wherein the at least one disintegrating excipient is a disintegrating excipient pre-mix that is present in an amount ranging from about 50% to about 80% by weight of the tablet (claim 8). F-melt type C is the most preferred disintegrating excipient for use in the tablets of the invention. Thus, in one embodiment the at least one disintegrating excipient is a disintegrating excipient pre-mix comprising mannitol, xylitol, anhydrous dibasic calcium phosphate, crospovidone and microcrystalline cellulose. In a further embodiment, the at least one disintegrating excipient pre-mix comprises F-melt type C (paragraph 0027). One of ordinary skill in the art would have been motivated to do so because Al Husban et al. teach that the tablets of the invention should contain a sufficient amount of the at least one disintegrating excipient in order for the tablet to disintegrate within a sufficiently short time. However, the amount of the at least one disintegrating excipient must not be so high as to cause difficulties in the manufacture of the tablet in view of the adhesiveness and/or cohesiveness of ticagrelor. It has been surprisingly found that tablets of the invention in which the at least one disintegrating excipient is a disintegrating excipient pre-mix that is present in an amount ranging from about 50% to about 80% by weight of the tablet have an acceptable disintegration time (e.g. less than 3 minutes) while simultaneously allowing the adhesiveness and/or cohesiveness of ticagrelor to be adequately countered during the manufacture of the tablets. Thus, in a further embodiment, the at least one disintegrating excipient is a disintegrating excipient pre-mix present in an amount ranging from about 50% to about 80% by weight of the tablet (paragraph 0028). One of ordinary skill in the art would have had a reasonable chance of success in combining the teachings of Chen Jen Chi et al. and Al Husban et al. because both references teach a tablet containing orally fast disintegrating layers.
With regard to the disintegrating time of (a) and (b) as recited in claims 8-9 respectively, Chen Jen Chi et al. teach that in another embodiment, the lozenge product further includes a second layer which is not a lozenge layer (e.g., a layer having orally disintegrating properties). In such an embodiment, upon administration of such a lozenge product having an additional orally disintegrating layer, the orally disintegrating layer quickly disintegrates in the mouth of the user, leaving the lozenge product to be sucked on by the user. It should be noticed that Chen Jen Chi et al. met the structure recited in claim 1. Therefore, the disintegrating property of each layer would be an innate property of the structure.
With regard to the pharmacokinetic parameter recitations of claims 13-14 the examiner reminds Applicant that Chen Jen Chi et al. clearly met the claimed structure of claim 1 which claims 13-14 depend from. The examiner reminds Applicant that 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). "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 or substantially similar structure, the properties applicant discloses and/or claims are necessarily present.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 1-4 and 6-16 are rejected under 35 U.S.C. 103 as being unpatentable over Chen Jen Chi et al. (EP2480215, previously provided to Applicant) in view of Chen (US 2013/0289079, IDS reference 11/30/2023).
Applicants’ claims
Applicant claims a tablet for intra-oral delivery of nicotine. Dependent claims thereof recite additional features.
Determination of the Scope and Content of the Prior Art
(MPEP 2141.01)
Chen Jen Chi et al. teach in certain embodiments, the chewing includes at least two layers, e.g., with different types and/or concentrations of amorphous carbohydrate polymers and/or other ingredients or different concentrations of pharmaceutically active agents. Such an embodiment is shown in FIGS. 2A-2D. In one embodiment, the lozenge is a bilayer form; wherein the first layer is a lozenge form and the second layer is a orally disintegrating form. In one embodiment the first layer is a lozenge form and the second layer is a lozenge form. In one embodiment the lozenge form layer is free of a material that reacts to RF heating. In one embodiment, the lozenge form layer or the orally disintegrating form layer is first compressed as a layer, then the powder blend is added to the compressed lozenge or compressed orally disintegrating form layer and the entire form is energized utilizing the RF apparatus (paragraph 0093). In another embodiment, the lozenge product further includes a second layer which is not a lozenge layer (e.g., a layer having orally disintegrating properties). In such an embodiment, upon administration of such a lozenge product having an additional orally disintegrating layer, the orally disintegrating layer quickly disintegrates in the mouth of the user, leaving the lozenge product to be sucked on by the user. In one such embodiment, the orally disintegrating layer contains one pharmaceutically active agent (e.g., an analgesic, antihistamine, decongestant, cough suppressant, or expectorant) and the lozenge product either does not contain a pharmaceutically active agent or contains a different pharmaceutically active agent (e.g., menthol) (paragraph 0096). As discussed above, the lozenge shape is manufactured by forming a powder blend containing an amorphous carbohydrate polymer and optionally nicotine and/or other pharmaceutically active agent(s) and/or excipients. Examples of such excipients include, but are not limited to, glidants, lubricants, sweeteners, flavors and aromatics, enhancers, coloring agents, preservatives, vitamins, minerals, fluoride, and tooth whitening agents, and mixtures thereof. One or more of the above ingredients may be present on the same particle of the powder blend (paragraph 0010). Suitable lubricants include, but are not limited to, long chain fatty acids and their salts, such as magnesium stearate and stearic acid, talc, glycerides waxes, and mixtures thereof (paragraph 0011). Suitable glidants include, but are not limited to, colloidal silicon dioxide. Examples of sweeteners include, but are not limited to, synthetic or natural sugars; artificial sweeteners such as saccharin, sodium saccharin, aspartame, acesulfame, thaumatin, glycyrrhizin, sucralose, dihydrochalcone, alitame, miraculin, monellin, and stevside; sugar alcohols such as sorbitol, mannitol, glycerol, lactitol, maltitol, and xylitol; sugars extracted from sugar cane and sugar beet (sucrose), dextrose (also called glucose), fructose (also called laevulose), and lactose (also called milk sugar); isomalt, salts thereof, and mixtures thereof. Examples of flavors and aromatics include, but are not limited to, essential oils including distillations, solvent extractions, or cold expressions of chopped flowers, leaves, peel or pulped whole fruit comprising mixtures of alcohols, esters, aldehydes and lactones; essences including either diluted solutions of essential oils, or mixtures of synthetic chemicals blended to match the natural flavor of the fruit (e.g., strawberry, raspberry and black currant); artificial and natural flavors of brews and liquors, e.g., cognac, whisky, rum, gin, sherry, port, and wine; tobacco, coffee, tea, cocoa, and mint; fruit juices including expelled juice from washed, scrubbed fruits such as lemon, orange, and lime; spear mint, peppermint, wintergreen, cinnamon, cacoe/cocoa, vanilla, liquorice, menthol, eucalyptus, aniseeds nuts (e.g., peanuts, coconuts, hazelnuts, chestnuts, walnuts, colanuts), almonds, raisins; and powder, flour, or vegetable material parts including tobacco plant parts, e.g., genus Nicotiana, in amounts not contributing significantly to the level of nicotine, and ginger (paragraphs 0012-0014). In one embodiment, the amount of amorphous carbohydrate polymer in the powder blend/lozenge shape/lozenge product is from about 50 percent to about 99.9 percent, by weight, such as from about 80 percent to about 95 percent by weight (paragraph 0017). In one embodiment, the powder blend/lozenge shape/lozenge product contains a smoking cessation compound(s) such as: nicotine and/or metabolites thereof, such as cotinine, etc., (paragraph 0019). In one embodiment, lozenge product includes the nicotine compound in an amount of from about 0.05 to about 12 mg calculated as the free base form of nicotine per lozenge product, such as from about 0.2-6 mg, such as from about 0.5-5 mg. This may in different embodiments include 0.05, 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 6, 7, 8, 9, 10, or 12 mg calculated as the free base form of nicotine per lozenge product (paragraph 0024). In one embodiment, the lozenge/powder blend/coating contains both nicotine and a buffering agent. In one embodiment, the lozenge is buffered such that upon administration of the lozenge, the pH of the saliva is transiently increased from about 0.2 to about 4 pH units, preferably from about 0.4 to about 2 pH units. The buffering is designed so as to achieve a transient buffering of the saliva of a subject during use of the lozenge product. As the change is transient, the pH will return to its normal value after a certain period of time (paragraph 0025). Examples of buffering agents include, but are not limited to, carbonates including carbonate, bicarbonate or sesquicarbonate, glycinate, phosphate, glycerophosphate or citrate of an alkali metal, such as potassium or sodium, or ammonium such as trisodium or tripotassium citrate, trisodium phosphate, disodium hydrogen phosphate, tripotassium phosphate, dipotassium hydrogen phosphate, calcium hydroxide, sodium glycinate, and trometamol (TRIS). Alkali metal carbonates, glycinates and phosphates are preferred buffering agents (paragraph 0026). The pharmaceutically active agent may be present in various forms. For example, the pharmaceutically active agent may be dispersed at the molecular level, e.g. melted, within the lozenge product, or may be in the form of particles, which in turn may be coated or uncoated. If the pharmaceutically active agent is in form of particles, the particles (whether coated or uncoated) typically have an average particle size of from about 1 to about 2000 microns. In one embodiment, such particles are crystals having an average particle size of from about 1 to about 300 microns. In another embodiment, the particles are granules or pellets having an average particle size of from about 50 to about 2000 microns, such as from about 50 to about 1000 microns, such as from about 100 to about 800 microns (paragraph 0047). The pharmaceutically active agent may be present in pure crystal form or in a granulated form prior to the addition of the taste masking coating. Granulation techniques may be used to improve the flow characteristics or particle size of the pharmaceutically active agents to make it more suitable for compaction or subsequent coating. Suitable binders for making the granulation include but are not limited to starch, polyvinylpyrrolidone, polymethacrylates, hydroxypropylmethylcellulose (which is Hypromellose), and hydroxypropylcellulose. The particles including pharmaceutically active agent(s) may be made by cogranulating the pharmaceutically active agent(s) with suitable substrate particles via any of the granulation methods known in the art. Examples of such granulation method include, but are not limited to, high sheer wet granulation and fluid bed granulation such as rotary fluid bed granulation (paragraph 0048). In one embodiment, a lubricant is added to forming cavity prior to the addition of the flowable powder blend. This lubricant may be a liquid or solid. Suitable lubricants include but are not limited to solid lubricants such as magnesium stearate, starch, calcium stearate, aluminum stearate and stearic acid; or liquid lubricants such as but not limited to simethicone, lecithin, vegetable oil, olive oil, or mineral oil. In certain embodiments, the lubricant is added at a percentage by weight of the lozenge of less than 5 percent, e.g. less than 2 percent, e.g. less than 0.5 percent (paragraph 0076). In one embodiment, the nicotine compound and/or the pharmaceutically active agent is in the form of a gel bead, which is liquid filled or semi-solid filled. The gel bead(s) are added as a portion of the powder blend. In one embodiment, the lozenge product of this invention has the added advantage of not requiring a strong compaction step, allowing for the use of liquid or semisolid filled particles or beads which are deformable since they will not rupture following the reduced pressure compaction step. These bead walls may contain gelling substances such as: gelatin; gellan gum; xanthan gum; agar; locust bean gum; carrageenan; polymers or polysaccharides such as but not limited to sodium alginate, calcium alginate, hypromellose, hydroxypropyl cellulose and pullulan; polyethylene oxide; and starches. The bead walls may further contain a plasticizer such as glycerin, polyethylene glycol, propylene glycol, triacetin, triethyl citrate and tributyl citrate. The pharmaceutically active agent may be dissolved, suspended or dispersed in a filler material such as but not limited to high fructose com syrup, sugars, glycerin, polyethylene glycol, propylene glycol, or oils such as but not limited to vegetable oil, olive oil, or mineral oil (paragraph 0091). Different bilayer tablet examples containing disintegrating layer and lozenge layer in mgs are taught in the examples.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP 2141.02)
Chen Jen Chi et al. do not specifically teach the buffering agents and polymer matrix ratios as recited in claim 6 and do not teach nicotine polacrilex as nicotine active agent as recited in claims 10-12. These deficiencies are cured by the teachings of Chen.
Chen teaches nicotine lozenge compositions comprising reduced levels of buffering agents from traditional nicotine lozenges and which provide optimal oral pH and prompt nicotine absorption in a smaller, more convenient dosage form (abstract). An oral lozenge composition comprising: a) a master granule component comprising: at least one an alkaline buffering agent selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium phosphate, potassium carbonate and potassium bicarbonate, and mixtures thereof; at least one dissolution modifier; and at least one diluent; and b) an extragranular component blended with the master granule component comprising nicotine polacrilex and at least one alkaline buffering agent selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium phosphate, potassium carbonate and potassium bicarbonate, and mixtures thereof (claim 1). Alkaline buffering agents suitable for use in the present invention include, but are not limited to, sodium carbonate, sodium bicarbonate, potassium phosphate, potassium carbonate and potassium bicarbonate. In one embodiment, the buffering agents are selected from potassium bicarbonate, sodium carbonate and mixtures thereof. The buffering agents are incorporated within the master granules as well as incorporated within the extra-granular space between said master granules. The total amount of buffer present in the compositions of the present invention is from about 5 mg to about 20 mg. In one embodiment the total amount of buffer present in the compositions of the present invention is from about 8 mg to about 12 mg. In one embodiment the ratio of nicotine polacrilex to total buffer is from about 3:1 to about 1:3 by total weight (paragraph 0025). As indicated above the alkaline buffering agents are incorporated both within the master granules (intragranular) and within the extragranular space between said master granules (extragranular). In general, the amount of buffering agent present in the compositions of the present invention, expressed as a ratio of intragranular buffering agent to extragranular buffering agent is from about 5:1 to about 1:5. In one embodiment, the ratio of intragranular buffering agent to extragranular buffering agent is about 1:1 (paragraph 0026). Dissolution modifiers suitable for use in the present invention include, but are not limited to, acacia, agar, alginic acid or a salt thereof, carbomer, carboxymethylcellulose, carrageenan, cellulose, chitosan, copovidone, cyclodextrins, ethylcellulose, gelatin, guar gum, hydroxyethyl cellulose, hydroxyethyl methylcellulose, hydroxypropyl cellulose, hypromellose, inulin, methylcellulose, pectin, polycarbophil or a salt thereof, polyethylene glycol, polyethylene oxide, polyvinyl alcohol, pullulan, starch, tragacanth, trehalose, xanthan gum and mixtures thereof. In one embodiment, the dissolution modifiers included within the formulations of the present invention are selected from the group consisting of alginic acid or a salt thereof, polycarbophil or a salt thereof, xanthan gum and mixtures thereof. In one embodiment, sodium alginate, calcium polycarbophil and xanthan gum are incorporated within the master granules of the present invention. The amount of dissolution modifier present in the master granules of the present invention is from about 10 mg to about 30 mg per lozenge, in another embodiment from about 15 mg to about 25 mg per lozenge (paragraph 0031). With regard to the amount of Hypromellose and xanthan gum one of ordinary skill in the art can easily calculate various ratios, for instance assuming Hypromellose is added in amount of about 10 mg to about 30 mg and xanthan gum is added in amounts of about 15 mg to about 25 mg, one can calculate 30/15 to 10/25 which is equivalent to 2:1 to 1:2.5 which will overlap with claimed amounts.
Finding of Prima Facie Obviousness Rational and Motivation
(MPEP 2142-2143)
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the instant invention to modify the teachings of Chen Jen Chi et al. by utilizing the buffering agents and polymeric matrixes in ratios as recited in claim 6 and also use nicotine polacrilex as the nicotine active agent because Chen teaches nicotine lozenge compositions comprising reduced levels of buffering agents from traditional nicotine lozenges and which provide optimal oral pH and prompt nicotine absorption in a smaller, more convenient dosage form (abstract). An oral lozenge composition comprising: a) a master granule component comprising: at least one an alkaline buffering agent selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium phosphate, potassium carbonate and potassium bicarbonate, and mixtures thereof; at least one dissolution modifier; and at least one diluent; and b) an extragranular component blended with the master granule component comprising nicotine polacrilex and at least one alkaline buffering agent selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium phosphate, potassium carbonate and potassium bicarbonate, and mixtures thereof (claim 1). Alkaline buffering agents suitable for use in the present invention include, but are not limited to, sodium carbonate, sodium bicarbonate, potassium phosphate, potassium carbonate and potassium bicarbonate. In one embodiment, the buffering agents are selected from potassium bicarbonate, sodium carbonate and mixtures thereof. The buffering agents are incorporated within the master granules as well as incorporated within the extra-granular space between said master granules. The total amount of buffer present in the compositions of the present invention is from about 5 mg to about 20 mg. In one embodiment the total amount of buffer present in the compositions of the present invention is from about 8 mg to about 12 mg. In one embodiment the ratio of nicotine polacrilex to total buffer is from about 3:1 to about 1:3 by total weight (paragraph 0025). As indicated above the alkaline buffering agents are incorporated both within the master granules (intragranular) and within the extragranular space between said master granules (extragranular). In general, the amount of buffering agent present in the compositions of the present invention, expressed as a ratio of intragranular buffering agent to extragranular buffering agent is from about 5:1 to about 1:5. In one embodiment, the ratio of intragranular buffering agent to extragranular buffering agent is about 1:1 (paragraph 0026). Dissolution modifiers suitable for use in the present invention include, but are not limited to, acacia, agar, alginic acid or a salt thereof, carbomer, carboxymethylcellulose, carrageenan, cellulose, chitosan, copovidone, cyclodextrins, ethylcellulose, gelatin, guar gum, hydroxyethyl cellulose, hydroxyethyl methylcellulose, hydroxypropyl cellulose, hypromellose, inulin, methylcellulose, pectin, polycarbophil or a salt thereof, polyethylene glycol, polyethylene oxide, polyvinyl alcohol, pullulan, starch, tragacanth, trehalose, xanthan gum and mixtures thereof. In one embodiment, the dissolution modifiers included within the formulations of the present invention are selected from the group consisting of alginic acid or a salt thereof, polycarbophil or a salt thereof, xanthan gum and mixtures thereof. In one embodiment, sodium alginate, calcium polycarbophil and xanthan gum are incorporated within the master granules of the present invention. The amount of dissolution modifier present in the master granules of the present invention is from about 10 mg to about 30 mg per lozenge, in another embodiment from about 15 mg to about 25 mg per lozenge (paragraph 0031). It is within the purview of one of ordinary skill in the art to optimize any amounts or ratios as they are result effective parameters. If applicants resort to argue the reference does not provide any motivation to select this specific combination, it must be remembered that “[w]hen 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.” KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious,” the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR at 1741. The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742. With regard to the amount of Hypromellose and xanthan gum one of ordinary skill in the art can easily calculate various ratios, for instance assuming Hypromellose is added in amount of about 10 mg to about 30 mg and xanthan gum is added in amounts of about 15 mg to about 25 mg, one can calculate 30/15 to 10/25 which is equivalent to 2:1 to 1:2.5 which will overlap with claimed amounts. Furthermore, in the case where the amount of ingredients, ratios, etc., "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) Furthermore, differences in concentration or size will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233,235 (CCPA 1955). One of ordinary skill in the art would have had a reasonable chance of success in combining the teachings of Chen Jen Chi et al. and Chen because both references teach lozenge compositions containing nicotine based compounds.
With regard to the disintegrating time of (a) and (b) as recited in claims 8-9 respectively, Chen Jen Chi et al. teach that in another embodiment, the lozenge product further includes a second layer which is not a lozenge layer (e.g., a layer having orally disintegrating properties). In such an embodiment, upon administration of such a lozenge product having an additional orally disintegrating layer, the orally disintegrating layer quickly disintegrates in the mouth of the user, leaving the lozenge product to be sucked on by the user. It should be noticed that Chen Jen Chi et al. disclose identical structure as recited in claim 1. Therefore, the disintegrating property of each layer would be an innate property of the structure. The examiner reminds Applicant that 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). "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 or substantially similar structure, the properties applicant discloses and/or claims are necessarily present.
With regard to the pharmacokinetic parameter recitations of claims 13-14 the examiner reminds Applicant that Chen Jen Chi et al. clearly met the claimed structure of claim 1 which claims 13-14 depend from. The examiner reminds Applicant that 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). "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 or substantially similar structure, the properties applicant discloses and/or claims are necessarily present.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
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/TIGABU KASSA/Primary Examiner, Art Unit 1619
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