The 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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 09/29/2025 has been entered.
Status of Application
Applicants' arguments/remarks filed 09/29/2025 are acknowledged. Claim 10 is newly added. Claim 2 is currently amended. Claims 2 and 7-10 are examined on the merits within and are currently pending.
Withdrawn Rejections
With applicant's amendments and with respect to applicant’s arguments/remarks filed 09/29/202, the rejection of claims 2 and 7-9 under 35 U.S.C. 103 over Shlieout et al. (WO 2007/020260 A2), Venkatesh et al., Zhang et al., and Gasco has been withdrawn in view of the amendment of claim 1.
Modified Rejections
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 non-obviousness.
Claims 2 and 7-10 are rejected under 35 U.S.C. 103 as being unpatentable over Shlieout et al. (WO 2007/020260 A2), Shlieout et al. (US 20140302000Al) and Venkatesh et al. ((WO 2011/140106 Al) in view of Zhang et al., (Zhang et al., Systematic Procedures for Formulation Design of Drug-Loaded Solid Lipid Microparticles: Selection of Carrier Material and Stabilizer. Ind. Eng. Chem. Res. 2008, 47, 6091–6100) and further in view of Gasco (5,250,236).
“Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).”
Claims 2 and 10,
Shlieout et al. (WO 2007/020260 A2) teach a pharmaceutical composition comprising a pharmacologically effective amount of pancreatin wherein the pancreatin is in the form of pancreatin micropellets, a dosage form suitable for oral administration containing said pharmacologically effective amount of pancreatin. (pg. 11, lines 32-36). Pancreatin micropellet cores can comprise: pancreatin, at least one pharmaceutically acceptable binding agent and at least one pharmaceutically acceptable excipient. (pg. 3, lines 10-13). Pancreatin micropellet cores can comprise pancreatin, at least one pharmaceutically acceptable binding agent and at least one pharmaceutically acceptable excipient. The pancreatin micropellets were graded, first with a 3.15 mm sieve (sieving of oversize grain > 3.15 mm) and then with a 0.7 mm sieve (sieving of undersize grain < 0.7 mm) and afterwards with a 1.25 mm sieve (sieving of oversize grain > 1.25 mm). (pg. 13, line 5-9), so the core diameter and length ranges are 0.7 mm-1.25 mm.
Examples of suitable enzyme-friendly organic solvents are acetone, chloroform,
dichloromethane or straight-chained or branched C1-4-alcohols, particularly methanol,
ethanol, 1-propanol, 2-propanol, 2-butanol, tert-butanol or mixtures of said solvents. 2-
propanol is the preferred enzyme-friendly organic solvent. (pg. 4, lines 20-23 and pg. 10, lines 3-6). Enzyme-friendly organic solvents facilitate mixing and other processing procedures and may afterwards be removed, for example, by drying. Typically, after removal of the enzyme-friendly organic solvents a certain amount of solvent remains in the pancreatin micropellet cores. The remaining solvent in the micro-pellet cores can comprise enzyme friendly organic solvents, water, or a mixture of enzyme-friendly organic solvents with water. If water is present as a solvent, this will typically have been present in the pancreatin which was used as the starting material. The amount of solvent present in the pancreatin micro-pellet cores after removal of the enzyme-friendly organic solvents is typically less than 5 % and normally less than 3 % by weight of the pancreatin micropellet core. (pg. 5, lines 10-19).
The process of Claim 1 wherein the binding agent is selected from the group consisting of: copolymers of polyoxyethylene-polyoxypropylene and mixtures of said organic polymers, (Claim 4, pg. 20), which include poloxamer and poloxamer 407.
Shlieout et al. (WO 2007/020260 A2) teach pancreatin, poloxamer 407, ethanol, in the core but cetyl alcohol in the coating, (Claim 9, 11, pg. 21), but do not teach cetyl alcohol in the core of micropellets.
Shlieout et al. (US 20140302000Al) teach orally administrable pharmaceutical compositions of lipase containing products, particularly pancreatin and pancreatin containing products. These oral pharmaceutical compositions contain a system which includes at least one surfactant and one co-surfactant and optionally a lipophilic phase, and are self-emulsifiable on contact with a hydrophilic and a lipophilic phase. The compositions according to the invention are suitable for treating or inhibiting maldigestion, especially maldigestion due to chronic exocrine pancreatic insufficiency, in mammals and humans. (Abs). "Polyoxyethylene-Polyoxypropylene Block Copolymers": The POE-POP block copolymers are a unique class of polymeric surfactants. The unique structure of the surfactants, with hydrophilic POE (PEO) and lipophilic POP (PPO) moieties in well-defined ratios and positions, is poloxamer, the formula: HO(C2H4O)a(C3H6O)b(C2H4O)a, where "a" and "b" denote the number of polyoxyethylene (poly(ethylene oxide)) and polyoxypropylene (poly(propylene oxide)) units, respectively, (0030), which includes poloxamer 407. Aliphatic alcohols with 12 to 22 carbon atoms are aliphatic C12-C22 alcohols. Preferably alcohols selected from the group consisting of lauryl alcohol (C12), myristyl alcohol (C14), cetyl alcohol (C16), stearyl alcohol (C18), arachidyl alcohol (C20), behenyl alcohol (C22), oleyl alcohol (C18), linoleyl alcohol (C18) and linolenyl alcohol (C18), individually or as a mixture, are used. Particularly preferably, the saturated alcohols are selected. (0050-0051). In conventional formulation pancreatin was moistened with Isopropanol. (0149).
Shlieout et al. (US 20140302000Al) teach pancreatin, poloxamer 407, cetyl alcohol, and solvent isopropanol.
Shlieout et al. (WO 2007/020260 A2) and Shlieout et al. (US 20140302000Al) do not teach percentages of the composition of pancreatin with excipients poloxamer 407, cetyl alcohol.
Venkatesh et al. teach pancreatin micropellet compositions. (Abs). The particles comprise, consist essentially of, or consist of 40-98 wt.% of digestive enzyme mixture; 2 -20 wt.% of a polymer. (pg. 8, lines 12-14). The polymer may be selected from polyethylene oxide. (pg. 8, line 22).
Venkatesh et al. do not teach cetyl alcohol and poloxamer 407 as excipients in the core of micropellets.
Gasco et al. teach different examples (Cols. 3-6) in Method for Producing Solid Lipid Microspheres Having a Narrow Size Distribution (Title), by different surfactants, lipids in water. (Abs). Such microspheres were prepared by mixing the active component with low melting materials, such as cetyl alcohol, polyoxyethylene glycol. (Col. 1, lines 43-45). Depending on solubility of surfactants, and lipids in water or Ethanol (taught by Shlieout et al. (WO 2007/020260 A2)), different ratios of surfactants and lipids were mixed and emulsified. Example 5, 0.4 g of purified egg lecithin and 0.6 g stearic acid (total 1g of lipid) are admixed with 1 mL Tween 20 (surfactant) in 10 mL water. The ratio of water: lipid:surfactant is 10: 1 : 1. It would be obvious that depending on solubility of surfactants, and lipids in water or Ethanol (taught by Shlieout et al. (WO 2007/020260 A2)), different ratios of surfactants and lipids were mixed and emulsified. Cetyl alcohol is not soluble in water and is soluble in ethanol, so ethanol is substituted for water to make sure they mixed completely. With ethanol density is 0.79g/mL so the ratio of ethyl alcohol, cetyl alcohol, poloxamer 407 in the following ratio 7.9 : 1: 1 = 1:0.13:0.13. Cetyl alcohol melting temperature is 49°C (120F), (https://en.wikipedia.org/wiki/Cetyl_alcohol), so the process should be carried out at temperature lower than 49°C. With up to 40%-98% pancreatin, taught by Venkatesh et al., 2% left for other excipients, and with 7.9:1:1 ratio of ethyl alcohol:lipid:surfactant, then cetyl alcohol and poloxamer percentage can be 0.5-4%.
Zhang et al. teach Clozapine-Loaded SLM Stability Using Different Stabilizers. Poloxamer 407 is one of the surfactants stabilize clozapine-loaded solid lipid microparticle (SLM)s. (pg. 6098, left col., 3rd par.). Cetyl alcohol, as a lipid, is used to prepare SLM. (pg. 6092, right col., 2nd par.). The carrier materials and clozapine were dissolved in ethanol to ensure that they mixed completely. (pg. 6097, right col., 4th par.).
Shlieout et al. (WO 2007/020260 A2) teach Preparation of pancreatin micropellet cores and pancreatin micropellets: 1. Preparation of uncoated pancreatin micropellet cores, which are solid lipid microparticles by mixing pancreatin and propanol and other ingredients and the temperature was less than 50C. (pg. 12, lines 30). United States Pat. App. No. 2004/0101562 (Maio) discloses microspheres of pancreatic enzymes with high stability and a production method thereof. A solid mixture, including one or more pancreatic enzymes, one or more hydrophilic low-melting polymers and other excipients, is heated at a temperature equal or higher than the melting temperature of said hydrophilic low-melting polymer while stirring. (pg. 1, lines 33-35-pg. 2, lines 1-2).
Shlieout et al. (WO 2007/020260 A2) teach pancreatin, poloxamer 407, ethanol, in the core.
Shlieout et al. (US 20140302000Al) teach the possible further configurations of the system to be used, consisting of surfactant, co-surfactant and lipophilic phase, correspond to the embodiments described above for the self-emulsifiable pharmaceutical preparation according
to the invention, which comprises such a system. (0131). a surfactant selected from the group consisting of polyoxyethylene- polyoxypropylene block copolymers, (0133), which is poloxamer. A co-surfactant selected from the group consisting of mono-acylglycerides, mono-ethers of glycerol, partial esters of propylenglycol, partial esters of polyglycerol, partial esters of ethyl diglycol, and mixtures thereof, and (0134) a lipophilic phase, which is represented by diand/ or triacylglycerides. (0135). Surfactant Gelucire® 50/13 or Gelucire® 44/14 was used in the examples 1A and 1B, by heating and mixing with pancreatin at 52°C or 48°C. (0140-0141). Pancreatin powder, Gelucire® 44/14 and Labrasol were mixed at 48°C. The conventional formulation was prepared according to the process disclosed in U.S. Pat. No. 5,378,462. 120 g pancreatin and 30 g PEG 4000 were initially dry-mixed and then moistened with 20 g isopropanol. The moist mixture was extruded and then rounded in a suitable rounder with the aid of paraffin oil. The resulting pellets were then dried. (0149).
Shlieout et al. (US 20140302000Al) teach pancreatin, poloxamer 407, cetyl alcohol, and solvent isopropanol.
Preparation:
Shlieout et al. (WO 2007/020260 A2) teach pancreatin, poloxamer 407, ethanol, in the core but cetyl alcohol in the coating, (Claim 9, 11, pg. 21).
Shlieout et al. (US 20140302000Al) teach pancreatin, poloxamer 407, cetyl alcohol, and solvent isopropanol.
Venkatesh et al. teach pancreatin micropellet compositions. (Abs). The particles comprise, consist essentially of, or consist of 40-98 wt.% of digestive enzyme mixture; 2 -20 wt.% of a polymer. (pg. 8, lines 12-14). The polymer may be selected from polyethylene oxide. (pg. 8, line 22).
Gasco teaches 7.9:1:1 ratio or 1:0.12:0.12 of ethyl alcohol:lipid:surfactant, then cetyl alcohol and poloxamer percentage can be 0.5-4%.
Zhang et al. teach Clozapine-Loaded SLM Stability Using Different Stabilizers. Poloxamer 407 is one of the surfactants stabilize clozapine-loaded solid lipid microparticle (SLM)s. (pg. 6098, left col., 3rd par.). Cetyl alcohol, as a lipid, is used to prepare SLM. (pg. 6092, right col., 2nd par.). The carrier materials and clozapine were dissolved in ethanol to ensure that they mixed completely. (pg. 6097, right col., 4th par.).
Zhang et al teach Systematic Procedures for Formulation Design of Drug-Loaded Solid Lipid Microparticles (SLM): Selection of Carrier Material and Stabilizer (Title). 3.3. Preparation of Clozapine-Loaded SLMs. 3.3.1. Materials and Experimental Methods: Ethanol: Lipid cetyl alcohol: Poloxamer are mixed the ratio 1: 0.13 : 0.13, taught by Gasco.
Mixing the drug with ethanol, and mixing with ingredients of a). Zhang et al. select drug Clozapine to prepare SLM, (pg. 6097, right col., 4th par.), but the steps are the same with pancreatin.
Shlieout et al. (WO 2007/020260 A2) teach the resulting mixture was extruded. The temperature was less than 50 °C, while pressing. The extruded mass was cut into extrudate fragments of approximately mm length by means of the cutting device. (pg. 12, line 30-34). U.S. Pat. No. 5,378,462 discloses pancreatin micropellets and their preparation with binding polymer and a lower alcohol, by extrusion and subsequent spheronisation. (pg. 1, lines 30-32).
Shlieout et al. (WO 2007/020260 A2) teach drying at a temperature from below 49 °C, the melting point for cetyl alcohol. (pg. 13, lines 5-6).
Shlieout et al. (WO 2007/020260 A2) teach: Enteric coating of pancreatin micropellet cores: (pg. 13, line 11). A pancreatin micropellet as defined in Claim 8, wherein the enteric coating comprises (claim 9, pg. 21): methacrylic acid ethyl methacrylate-copolymer,
Venkatesh et al. teach the coating agents are polyethylene glycol (PEG4000) (Macrogol) (pg. 15, lines 4-6), talc (pg. 6, line 15), methacrylic acid-methylmethacrylate copolymers (with ratio 1:1, Eudragit L 100). (pg. 15, lines 1-2).
It would have been obvious to one of ordinary skill in the art before effective filing date of the invention to apply method of production of pancreatin microgranules with coating taught by Shlieout et al. (WO 2007/020260 A2) and Shlieout et al. (US 20140302000Al) with the core of solid lipid microparticles comprising ethyl alcohol, cetyl alcohol and poloxamer 407 taught by by Shlieout et al. (WO 2007/020260 A2) and Shlieout et al. (US 20140302000Al), the preparation steps taught by Shlieout et al. (WO 2007/020260 A2) and Shlieout et al. (US 20140302000Al), Zhang et al. and with ratios of these ingredients taught by Gasco, and coated by plasticizers taught by Shlieout et al. (WO 2007/020260 A2) and Venkatesh et al. since they have combined solid lipid core with surfactant and coating in pancreatin microgranules to improve bioavailability of the drug.
With regard to claim 7,
Shlieout et al. (WO 2007/020260 A2) teach a pharmaceutical composition comprising a pharmacologically effective amount of pancreatin wherein the pancreatin is in the form of pancreatin micropellets, a dosage form suitable for oral administration containing said pharmacologically effective amount of pancreatin. (pg. 11, lines 32-36). Pancreatin micropellet cores can comprise: pancreatin, at least one pharmaceutically acceptable binding agent and at least one pharmaceutically acceptable excipient. (pg. 3, lines 10-13). Pancreatin micropellet cores can comprise pancreatin, at least one pharmaceutically acceptable binding agent and at least one pharmaceutically acceptable excipient. The pancreatin micropellets were graded, first with a 3.15 mm sieve (sieving of oversize grain > 3.15 mm) and then with a 0.7 mm sieve (sieving of undersize grain < 0.7 mm) and afterwards with a 1.25 mm sieve (sieving of oversize grain > 1.25 mm). (pg. 13, line 5-9), so the core diameter and length ranges are 0.7 mm-1.25 mm.
Examples of suitable enzyme-friendly organic solvents are acetone, chloroform,
dichloromethane or straight-chained or branched C1-4-alcohols, particularly methanol,
ethanol, 1-propanol, 2-propanol, 2-butanol, tert-butanol or mixtures of said solvents. 2-
propanol is the preferred enzyme-friendly organic solvent. (pg. 4, lines 20-23). Enzyme-friendly organic solvents facilitate mixing and other processing procedures and may afterwards be removed, for example, by drying. Typically, after removal of the enzyme-friendly organic solvents a certain amount of solvent remains in the pancreatin micropellet cores. The remaining solvent in the micro-pellet cores can comprise enzyme friendly organic solvents, water, or a mixture of enzyme-friendly organic solvents with water. If water is present as a solvent, this will typically have been present in the pancreatin which was used as the starting material. The amount of solvent present in the pancreatin micro-pellet cores after removal of the enzyme-friendly organic solvents is typically less than 5 % and normally less than 3 % by weight of the pancreatin micropellet core. (pg. 5, lines 10-19).
The process of Claim 1 wherein the binding agent is selected from the group consisting of: copolymers of polyoxyethylene-polyoxypropylene and mixtures of said organic polymers, (Claim 4, pg. 20), which include poloxamer and poloxamer 407.
Shlieout et al. (WO 2007/020260 A2) teach cetyl alcohol in the coating, (Claim 9, 11, pg. 21), but do not teach cetyl alcohol in the core of micropellets.
Shlieout et al. (US 20140302000Al) teach orally administrable pharmaceutical compositions of lipase containing products, particularly pancreatin and pancreatin containing products. These oral pharmaceutical compositions contain a system which includes at least one surfactant and one co-surfactant and optionally a lipophilic phase, and are self-emulsifiable on contact with a hydrophilic and a lipophilic phase. The compositions according to the invention are suitable for treating or inhibiting maldigestion, especially maldigestion due to chronic exocrine pancreatic insufficiency, in mammals and humans. (Abs). "Polyoxyethylene-Polyoxypropylene Block Copolymers": The POE-POP block copolymers are a unique class of polymeric surfactants. The unique structure of the surfactants, with hydrophilic POE (PEO) and lipophilic POP (PPO) moieties in well-defined ratios and positions, is poloxamer, the formula: HO(C2H4O)a(C3H6O)b(C2H4O)a, where "a" and "b" denote the number of polyoxyethylene (poly(ethylene oxide)) and polyoxypropylene (poly(propylene oxide)) units, respectively. (0030). Aliphatic alcohols with 12 to 22 carbon atoms are aliphatic C12-C22 alcohols. Preferably alcohols selected from the group consisting of lauryl alcohol (C12), myristyl alcohol (C14), cetyl alcohol (C16), stearyl alcohol (C18), arachidyl alcohol (C20), behenyl alcohol (C22), oleyl alcohol (C18), linoleyl alcohol (C18) and linolenyl alcohol (C18), individually or as a mixture, are used. Particularly preferably, the saturated alcohols are selected. (0050-0051)
Shlieout et al. (WO 2007/020260 A2) and Shlieout et al. (US 20140302000Al) do not teach percentages of the composition of pancreatin with excipients.
Venkatesh et al. teach pancreatin micropellet compositions. (Abs). The particles comprise, consist essentially of, or consist of 40-98 wt.% of digestive enzyme mixture; 2 -20 wt.% of a polymer. (pg. 8, lines 12-14). The polymer may be selected from polyethylene oxide. (pg. 8, line 22).
Venkatesh et al. do not teach cetyl alcohol and poloxamer 407 as excipients in the core of micropellets.
Zhang et al. teach Clozapine-Loaded SLM Stability Using Different Stabilizers. Poloxamer 407 is one of the surfactants stabilize clozapine-loaded solid lipid microparticle (SLM)s. (pg. 6098, left col., 3rd par.). Cetyl alcohol, as a lipid, is used to prepare SLM. (pg. 6092, right col., 2nd par.). The carrier materials and clozapine were dissolved in ethanol to ensure that they mixed completely. (pg. 6097, right col., 4th par.).
Gasco et al. teach different examples (Cols. 3-6) in Method for Producing Solid Lipid Microspheres Having a Narrow Size Distribution (Title), by different surfactants, lipids in water. (Abs). Depending on solubility of surfactants, and lipids in water or Ethanol (taught by Zhang), different ratios of surfactants and lipids were mixed and emulsified. Example 5, 0.4 g of purified egg lecithin and 0.6 g stearic acid (total 1g of lipid) are admixed with 1 mL Tween 20 (surfactant) in 10 mL water. The ratio of water: lipid:surfactant is 10: 1 : 1. It would be obvious that depending on solubility of surfactants, and lipids in water or Ethanol (taught by Zhang), different ratios of surfactants and lipids were mixed and emulsified. Cetyl alcohol is not soluble in water and is soluble in ethanol, so ethanol is substituted for water to make sure they mixed completely. With ethanol density is 0.79g/mL so the ratio of ethyl alcohol, cetyl alcohol, poloxamer 407 in the following ratio 7.9 : 1: 1 = 1:0.13:0.13. Cetyl alcohol melting temperature is 49°C (120F), (https://en.wikipedia.org/wiki/Cetyl_alcohol), so the process should be carried out at temperature lower than 49°C. With up to 40%-98% pancreatin, taught by Venkatesh et al., 2% left for other excipients, and with 7.9:1:1 ratio of ethyl alcohol:lipid:surfactant, then cetyl alcohol and poloxamer percentage can be 0.5-4%.
Shlieout et al. (WO 2007/020260 A2) teach pancreatin micropellets which are enteric-coated pancreatin micropellet cores. For enteric coating, any enteric coating can be used which
is suitable for delivery of the pancreatin micropellet cores to the upper intestine and compatible
with the pancreatin micropellet cores. Examples are enteric coatings known from U.S. Pat. No. 5,378,462 or commercially available enteric coatings like Eudragit™ polymers. (polymethacrylates) (pg. 7, lines 1-6), Dimethicone (pg. 14, Table 1.
Venkatesh et al. teach The micropellets may have one or more coatings layers, which comprise neutral methacrylic ester copolymers, ammonio-methacrylate copolymers, and mixtures thereof. (pg. 8, lines 19-27).
With regard to claim 8,
Shlieout et al. teach (WO 2007/020260 A2)a pharmaceutical composition comprising a pharmacologically effective amount of pancreatin wherein the pancreatin is in the form of pancreatin micropellets manufactured according to the processes described herein in a dosage form suitable for oral administration containing said pharmacologically effective amount of pancreatin. (pg. 11, line 32-36).
Shlieout et al. (US 20140302000Al) teach orally administrable pharmaceutical compositions of lipase containing products, particularly pancreatin and pancreatin containing products. These oral pharmaceutical compositions contain a system which includes at least one surfactant and one co-surfactant and optionally a lipophilic phase, and are self-emulsifiable on contact with a hydrophilic and a lipophilic phase. (Abs).
With regard to claim 9,
Shlieout et al. (WO 2007/020260 A2) teach pancreatin micropellets are useful for the prophylaxis and/or treatment of various medical conditions and digestive disorders including pancreatic exocrine insufficiency of different origins like maldigestion, and/or for the prophylaxis and/or treatment of pancreatitis, cystic fibrosis, diabetes type I and/or diabetes type II in mammals such as humans. (pg. 11, lines 6-10).
Shlieout et al. (US 20140302000Al) teach the compositions according to the invention are suitable for treating or inhibiting maldigestion, especially maldigestion due to chronic exocrine pancreatic insufficiency, in mammals and humans. (Abs).
Response to Arguments
Regarding Allowable Subject Matter: previously allowable subject matter of claims 2-3, the Office Action asserts "claim 2 was also further amended with additional subject matter, and is changed from a composition to a method of production, which requires more research of prior arts, which lead to new rejections." Applicant respectfully submits independent claim 2 has been rewritten as a composition claim, which was previously deemed allowable subject matter. Accordingly, Applicant respectfully submits that the claims are in complete condition for allowance.
Claim 2 is amended to composition, but still has preparation method in it. In addition, new prior arts are found to reject claim 2 and other dependent claims. Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
Rejections under 35 U.S.C. § 103
Applicants argue that the previous Office Action dated September 05, 2024 stated "Claim 2 recites very specific excipients and narrow range of ratios that have not been found in the prior art." Further, as acknowledged in the present Office Action, Shileout and Venkatesh fail to disclose or suggest ethyl alcohol, cetyl alcohol, and poloxamer 407 as excipients in the core of micropellets. As such, the Office Action looks to Zhang to cure said deficiency.
Applicant's arguments have been fully considered but they are not persuasive, since the amended claims allow the new search of prior arts, which explained in detailed in the rejection of claim 2 above.
Shlieout et al. (US 20140302000Al) teach pancreatin, poloxamer 407, cetyl alcohol, and solvent isopropanol.
Shlieout et al. (WO 2007/020260 A2) teach pancreatin, poloxamer 407, ethanol, in the core but cetyl alcohol in the coating, (Claim 9, 11, pg. 21).
Venkatesh et al. teach pancreatin micropellet compositions. (Abs). The particles comprise, consist essentially of, or consist of 40-98 wt.% of digestive enzyme mixture; 2 -20 wt.% of a polymer. (pg. 8, lines 12-14). The polymer may be selected from polyethylene oxide. (pg. 8, line 22).
Gasco teaches 7.9:1:1 ratio or 1:0.12:0.12 of ethyl alcohol:lipid:surfactant, then cetyl alcohol and poloxamer percentage can be 0.5-4%.
Shlieout et al. (WO 2007/020260 A2), Shlieout et al. (US 20140302000Al), teach pancreatin, poloxamer 407, cetyl alcohol, and solvent ethanol, Venkatesh et al. teach 40-98 wt.% of digestive enzyme mixture; 2 -20 wt.% of a polymer. and Gasco teach 1:0.12:0.12 of ethyl alcohol:lipid:surfactant, then cetyl alcohol and poloxamer percentage can be 0.5-4%. Zhang does not need to cure the deficiency.
Applicants argue that Zhang fails to cure the deficiencies of Shileout and the other secondary references. For instance, the Office Action states, "Zhang et al. teach Clozapine Loaded SLM Stability Using Different Stabilizers. Poloxamer 407 is one of the surfactants
stabilize clozapine-loaded solid lipid microparticle (SLM)s. The formulation consists of 5 wt
% lipid, 2 wt % stabilizer. (pg. 6098, left col., 3rd par.). Cetyl alcohol, as a lipid, is used to
prepare SLM. (pg. 6092, right col., 2nd par.). Poloxamer 407 is a stabilizer. (pg. 6094, left col.,
2nd last par.)." See Office Action, pages 6-7. Applicant respectfully disagrees. Turning to the
particular sections of Zhang in which the Office Action relies, Zhang specifically teaches
"Compritol as the carrier materials and soybean lecithin/ bile salt (mass ratio of 2:1) as the
stabilizer. The formulation consists of 5 wt% lipid, 2 wt% stabilizer, 5 wt% clozapine (relative
to the lipid), and water." (See Zhang, page 6098). In other words, when read in context, 2 wt.%
stabilizer clearly corresponds to 2 wt.% soybean lecithin/ bile salt as a stabilizer. Further, when
employed as a stabilizer, formulations in Zhang contain 5 wt.% poloxamer 407 (See Zhang,
page 6098). Zhang teaches that "[w]hen the molar content of clozapine reaches 5%, poloxamer
407 totally envelops on the particle surface." (See Zhang, page 6097). Nowhere does Zhang
disclose or suggest a pharmaceutical composition comprising inter alia poloxamer 407 in the
amount from 1.0 wt% up to 2.1 wt%, as set forth in amended independent claims 2 and 7.
Applicant's arguments have been fully considered but they are not persuasive, since the basis for 103 rejection is that no one reference has to teach all the claim limitations for an obviousness rejection and therefore several references are combined to render the claims obvious. One with ordinary skill in the art can learn from and select specific parts of several prior arts’ teachings before the effective filing date of the invention to achieve better outcome results even though some prior arts may teach more and may teach different things. Each prior art above teach more and teach other things also, but one with skill in the art would and should be able to select some from teach as explained in details in the rejections above.
Conclusion
No claim is allowed at this time.
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/NGOC-ANH THI NGUYEN/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615