DETAILED ACTION
Status of Application
Claims 1-40 are presented for examination on the merits. The following rejections are made.
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.
Claims 1-11 and 13-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Aimi et al. (US 2009/0280148) in view of Allen et al. (US 2014/0333003).
Aimi describes a method casein nanoparticle stabilized by being an aqueous liposomal dispersion.
Aimi’s method requires mixing casein (see instant claim 13) into a basic (i.e. alkaline) aqueous medium (see claim 1), adding an active substance to the alkaline mixture (see claim 1) and then acidifying the alkaline solution by adding to an acidic solution so as to produce a pH that is 1 pH unit or more away from the isoelectric point to 8 (see claim 1 and [0051]) (see instant claims 1 and 18). Although Aimi does not teach a final pH of 4.6 or less post acidification, such would have been obvious given that the general framework of the claimed method is described by the reference. See MPEP 2144.05(II)(A) regarding optimization of general conditions described by the prior art.
Example 1 of Aimi teaches that casein is to be present in a concentration of about 2% (20 mg/1036mg; density of water and phosphate buffer assumed 1g/mL; math not shown). Using this as a starting point, one of ordinary skill in the art would readily modulate the amount of casein so as to identify what concentration of casein works best in the method of producing the liposomal dispersion. However, it is again noted that Aimi teaches a protein concentration which overlaps with that of instant claim 14.
Example 1 also teaches that the active agent (chondroitin sulfate) is provided in an amount of 2 mg to a solution volume of 1 mL. It is observed that this concentration is lower than that specified by instant claim 1 (10-100 mg/mL). However, Aimi teaches that the active agent may be present in the method in an amount of 0.1-100% by weight relative to casein (see [0020]). Thus, the amount of active agent included in the method would be adjustable according to the amount of casein. Referring back to Example 1, there the active agent is present in an amount of 10% relative to casein. In the circumstance that the active were present in an amount of 100% relative to casein, this would result in 20 mg of the active resulting in a concentration of 20mg/mL which is within the claimed range. See MPEP 2144.05(I) regarding obviousness of similar ranges and MPEP2144.05(II)(A) regarding optimization of general conditions described by the prior art.
Aimi teaches that the solution is made alkaline by the addition of bases such as sodium hydroxide and potassium hydroxide (see [0047]) (see instant claim 9) and that the solution may be made acidic by addition of hydrochloric acid (see Example 8 and [0047]) (see instant claim 17).
Exemplified active agents include beta-carotene (a carotenoid), astaxanthin (a carotenoid), coenzyme Q10 and retinoic acid (see [0015, 0055]) (see instant claims 4, 5, 7 and 8). It is noted that retinoic acid is a carboxylic acid which is defined by the claims as being a functional group with a labile acid hydrogen (see instant claims 2 and 3).
The addition of the casein to the basic aqueous medium may be supplemented with additional substances such as lipids (see [0064]) and polysaccharides such as gellan gum and xanthan gum (see [0066]) (see instant claim 19). Exemplified lipids include olive oil and soybean oil (see [0064]) (see instant claim 15) as well as phospholipids such as diphoophatidylglycerol and dimyristoylphosphatidylcholine (see [0062]) (see instant claims 10 and 11). Regarding the concentration of the added oil to the method, Aimi teaches that the oil may be added in an amount of 0.1-100% with respect to casein (see [0023]). Aimi is silent regarding the total contribution of the oil in the method as set forth by instant claim 16. However, as casein is present in Example 1 in a concentration of about 2% (see above) and knowing that the oil is present in in amount of 0.1-100% relative to casein, this would result in a range of between 0.2-2% (for the oil component in the method) which overlaps with that claimed. See MPEP 2144.05(I).
The method may include rendering the liposomal composition a powder via spray or freeze drying (see [0006, 0082]) (see instant claim 39).
Although Aimi teaches the liposomal method as including mixing at high speed (e.g. 300 rpm), Aimi fails to teach the mixing being that of shear mixing.
Allen is directed to liposomal compositions and methods of making. It is taught that the liposomes are homogenized in solution by shear mixing wherein high shear mixing yields predominatly unilamellar liposomes whereas low shear mixing yields combinatinos of unilamellar and multilamellar liposomes (see [0044]). It would have been an obvious modification of Aimi’s mixing and homogenization method step to employ shear mixing as the means of mixing with a reasonable expectation for success. See MPEP 2143(I)(A) which states that combining prior art elements according to known methods to yields predictable results is indicative of obviousness.
Like Aimi, Allen’s liposomes are use to deliver various botanical and nutraceutical agents. Exemplified agents include beta-carotene, retinol, vitamin E, thiamine, niacinamide, vitamin K, flavonoids, resveratrol, extracts of ginseng and garlic and so on (see [0051, 0052]) (see instant claim 6). Including these agents, such as ginseng extract, into Aimi’s liposome method would have been obvious given the overlap of the agents described by both references.
Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was filed, as evidenced by the references, especially in absence of evidence to the contrary.
Claim 12 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Aimi et al. (US 2009/0280148) in view of Allen et al. (US 2014/0333003) as applied to claims 1-11 and 13-19 above, and further in view of Kurzrock et al. (US 2008/0138400).
Aimi suggests their liposomal method comprise phosphatidylglycerols and phosphatidylcholine (e.g. dimyristoylphosphatidylcholine), but fails to teach the method as comprising the phosphatidylglycerol dimyristoylphosphatidylglycerol.
Kurzrock is directed to curcumin liposomes and their methods of production. It is taught that liposomes are a product of the presence of vesicle-forming lipids such as phosphoglycerides including phosphatidylcholine, such as dimyristoylphosphatidylcholine (see [0059]), and phosphatidylglycerols, such as dimyristoylphosphatidylglycerol (see [0065]) (see instant claim 12). It would have been obvious to identify and include the lipid dimyristoylphosphatidylglycerol for inclusion into Aimi’s method as said lipid is a known alternative to those described by Aimi. See MPEP 2144.06(I) regarding combining equivalents known for same purpose.
Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was filed, as evidenced by the references, especially in absence of evidence to the contrary.
Claims 20-30 and 32-38 is/are rejected under 35 U.S.C. 103 as being unpatentable over Aimi et al. (US 2009/0280148) in view of Allen et al. (US 2014/0333003) and Kanazawa (US 2010/0143424).
Aimi and Allen are relied upon for disclosure described in the rejection of claims 1-11 and 13-19 under 35 U.S.C. 103. That rejection is fully incorporated here.
Allen’s liposome method are to include various botanical and nutraceutical agents. Exemplified agents include beta-carotene, retinol, vitamin E, thiamine, niacinamide, vitamin K, flavonoids, resveratrol, extracts of ginseng and garlic and so on (see [0051, 0052]) (see instant claims 25 and 27). Including these agents, such as ginseng extract, into Aimi’s liposome Aimi and Allen fail to teach their method as dissolving the water-insoluble compound (e.g. active agent) in an acidic aqueous solution, adding an amphiphilic lipid, adding an edible oil, subjecting mixture to high shear mixing and then neutralizing the acidic solution.
Kanazawa describes a method casein nanoparticle stabilized by being an aqueous liposomal dispersion.
Kanazawa’s method requires mixing casein (see instant claim 32) into an acidic aqueous medium (see claim 13), adding an active substance to the acidic mixture (see claim 14) and then increasing the pH of the acidic solution to a final pH that is +/- 0.5 pH units away from the isoelectric point (see claims 12-13) (see instant claims 20). Although Kanazawa does not teach a final pH of 4.6 or less post alkalinization, such would have been obvious given that the general framework of the claimed method is described by the reference. See MPEP 2144.05(II)(A) regarding optimization of general conditions described by the prior art.
Regarding the pH in the method, as it was known that casein nanoparticles can be reliably produced going from an acidic pH to alkaline (Kanazawa) or from alkaline to acidic (Aimi), one of ordinary skill would envisage both as obvious variants of one another and recognize that Aimi’s method could be modified to flip the initial and final pH of the process and still achieve success.
Example 1 of Kanzawa teaches that casein is to be present in a concentration of about 1% (100 mg casein/10100mg solution; density of citric acid solution assumed 1g/mL; math not shown). Using this as a starting point, one of ordinary skill in the art would readily modulate the amount of casein so as to identify what concentration of casein works best in the method of producing the liposomal dispersion. However, it is again noted that Kanazawa teaches a protein concentration which overlaps with that of instant claim 33.
Kanazawa teaches that the solution made be made acidic by addition of made acidic by addition of hydrochloric acid (see [0042]) (see instant claim 28) and alkaline by addition of bases such as sodium hydroxide and potassium hydroxide (see [0042]) (see instant claim 36).
Exemplified active agents include beta-carotene (a carotenoid), astaxanthin (a carotenoid), coenzyme Q10, retinoic acid and tetracycline (see [0050, 0052]) (see instant claims 21, 23, 24 and 26). It is noted that tetracycline has an imide group (see instant claim 22).
The addition of the casein to the acidic aqueous medium may be supplemented with additional substances such as lipids (see [0060, 0063]) and polysaccharides such as gellan gum and xanthan gum (see [0065]) (see instant claim 38). Exemplified lipids include olive oil and soybean oil (see [0063]) (see instant claim 34) as well as phospholipids such as dimyristoylphosphatidylcholine (see [0060]) (see instant claims 29 and 30).
Kanazawa is silent as to the concentration of the active and the concentration of oil in their method, however, given the similarity between Aimi and Kanazawa one would use Aimi’s method as a guide for identifying suitable concentrations of additives. For example, Aimi, as described above, teaches that the oil can be present in an amount of 0.2-2% and such would have provided a starting point for Kanazawa’s method. The analysis of Aimi’s active agent concentration is the method is also applied here.
Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was filed, as evidenced by the references, especially in absence of evidence to the contrary.
Claim 31 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Aimi et al. (US 2009/0280148) in view of Allen et al. (US 2014/0333003) and Kanazawa (US 2010/0143424) as applied to claims 1-11 and 13-19 above, and further in view of Kurzrock et al. (US 2008/0138400).
Aimi and Kanazawa both teach their liposomal methods as comprising phosphatidylglycerols and phosphatidylcholine (e.g. dimyristoylphosphatidylcholine), but fail to teach the phosphatidylglycerol dimyristoylphosphatidylglycerol.
Kurzrock is directed to curcumin liposomes and their methods of production. It is taught that liposomes are a product of the presence of vesicle-forming lipids such as phosphoglycerides including phosphatidylcholine, such as dimyristoylphosphatidylcholine (see [0059]), and phosphatidylglycerols, such as dimyristoylphosphatidylglycerol (see [0065]) (see instant claim 12). It would have been obvious to identify and include the lipid dimyristoylphosphatidylglycerol for inclusion into obvious method as said lipid is a known alternative to those described by Aimi. See MPEP 2144.06(I) regarding combining equivalents known for same purpose.
Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was filed, as evidenced by the references, especially in absence of evidence to the contrary.
Claim 39 is rejected under 35 U.S.C. 103 as being unpatentable over Aimi et al. (US 2009/0280148) in view of Allen et al. (US 2014/0333003) as applied to claims 1-11 and 13-19 above, and further in view of Collins (US 5567433).
While teaching producing a powder, Aimi and Allen fail to teach grinding the liposomal composition to produce the powder.
Collins teaches that liposome composition can be render into a powder by spray drying, vacuum drying or grinding (see column 4, lines 60-66). It would have been obvious to modify the obvious method to produce a liposomal powder by the method of grinding.
Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was filed, as evidenced by the references, especially in absence of evidence to the contrary.
Claim 40 is rejected under 35 U.S.C. 103 as being unpatentable over Aimi et al. (US 2009/0280148) in view of Allen et al. (US 2014/0333003) and Kanazawa (US 2010/0143424) as applied to claims 20-30 and 32-38 above, and further in view of Collins (US 5567433).
While teaching producing a powder, Aimi, Allen and Kanazawa fail to teach grinding the liposomal composition to produce the powder.
Collins teaches that liposome composition can be render into a powder by spray drying, vacuum drying or grinding (see column 4, lines 60-66). It would have been obvious to modify the obvious method to produce a liposomal powder by the method of grinding.
Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was filed, as evidenced by the references, especially in absence of evidence to the contrary.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KYLE A PURDY whose telephone number is (571)270-3504. The examiner can normally be reached from 9AM to 5PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Bethany Barham, can be reached on 571-272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KYLE A PURDY/Primary Examiner, Art Unit 1611
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