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 .
Status of Application
Applicants' arguments/remarks filed 12/09/2025 are acknowledged. Claims 1 and 8-9 are currently amended. Claims 1-3, 5-6 and 8-10 are examined on the merits within and are currently pending.
Withdrawn Rejections
With applicants' amendment filed 07/14/2025 and with respect to the applicants' arguments/remarks:
The rejection of Claims 1-3 and 5-6 under 35 U.S.C. 103 over Sato et al. and Berkland et al. has been withdrawn due to the amendment of claim 1;
The rejection of Claims 1, 3 and 8-10 under 35 U.S.C. 103 over Sato et al., Berkland et al. and Liu et al. and Berbely et al. has been withdrawn due to the amendment of claims 1 and 8-9.
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 1-3 and 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over Sato et al. (JP 2014114272 A), in view of Tokudome et al. (Tokudome et al. A new strategy for the passive skin delivery of nanoparticulate, high molecular weight hyaluronic acid prepared by a polyion complex method. Scientific Reports: 8:2336, 2018).
Claim 1,
Sato et al. teach the present invention to be applied to the production of cosmetics using a polymer compound as an active ingredient, (pg. 12, 5th par.), comprising a citrate buffer solution (aqueous), having a size of 100 nm or less (pg. 4, par. 9th-11th).
The pH of the citrate buffer is preferably 7.0 or less, more preferably 6.8 or less, and more preferably 6.5 or less. The lower limit of the pH is not particularly limited, but when used for, for example, an external preparation for skin, it is preferable to set the lower limit to about pH 5.5 from the viewpoint of irritation to the skin. The citrate concentration in the citrate buffer is preferably 0.1 to 10 mM. (pg. 4, 11th and 12th par.). The ionic strength based on the citrate salt only (as in claim 1 of the instant application), as pH in between 6.5-7, the citrate buffer, which has pKa1
3.13, pKa2 4.76 and pKa 3 6.4, is ionized to 3H+ and citrate-3. The ionic strength:
I = 1/2 * Σ(Ci * Zi^2)
For 0.1x10-3 concentration: ½(0.1x3x12 + 0.1x32) = 0.6 x 10-3
For 10x10-3 concentration: ½(10x3x12 + 10x32) = 60 x 10-3 = 0.06 > 0.01 and 0.06 < 1.
Sato et al. do not teach hyaluronic acid at a ratio of more than 90% by mass or more, based on the total polymer amount contained in the hyaluronic acid particle, and the content ratio of the other polymer component other than the hyaluronic acid in the hyaluronic acid particle is 10% by mass or less, based on the total polymer amount contained in the hyaluronic acid particle.
Tokudome et al. teach to deliver hyaluronic acid into the skin beyond the limit of skin penetration. Hyaluronic acid nanoparticles are prepared by mixing negatively charged HA with positively charged protamine (PRT). (pg. 2, 3rd par.). HA-PRT NPs are prepared at different ratios of HA:PRT by mixed them at different rations 10:90-90:10, to have NPs from 101.8-151.5 nm diameter. (Table 1, pg. 3). Protamine is considered a small protein or, more accurately, a small polycationic peptide. It is generally categorized as a low molecular weight, arginine-rich protein, with an average molecular weight of approximately 4,000 to 6,000 Daltons (Da), though some forms can range from 5.5 to 13.0 kDa. With a positive polypeptide, or a positive polymer, it can form nanoparticles with HA for skin application.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare cosmetic compositions, comprising a citrate buffer solution (aqueous), with ionic strength in between 0.1 and 1, taught by Sato et al., and to have HA nanoparticle less than 200 nm, with 90% HA, taught by Tokudome et al., since they have proven it would be feasible to do so.
With regard to claim 2,
Sato et al. teach anionic polymer, Preferably it is 100 to 2000 kDa. (pg. 2, 8th par.).
Tokudome et al. teach anionic HA ( average molecular weight: 1,200 kDa. (pg. 2, 5th par.).
With regard to claim 3,
Sato et al. teach citric buffer is an organic salt. (pg. 4, 11th and 12th par.).
With regard to claim 5,
(1) Preparation of hyaluronan solution A hyaluronan solution is prepared using a citrate buffer (pH 6.5)as a solvent.
The concentration of hyaluronan in the mixed solution is 1 to 2000 µg / ml. (pg. 5, 6th
last par.), which is equal 0.001g-0.1g/100g or 0.001-0.1 wt.%.
With regard to claim 6,
Sato et al. teach
The concentration of hyaluronan in the mixed solution is preferably 1 to 2000 µg / mL, (pg. 6th last par.), which is <0.2wt%.
The concentration of the anionic polymer with respect to the solution after mixing is preferably 0.2 to 50 µg / mL, (pg. 4th last par.), which is <.0.005 wt. %.
The concentration of chitosan with respect to the solution after mixing preferably it is 1-1000 microgram / mL, (pg. 5th last par.), which is <0.1wt%.
Citrate buffer (pH 6.5): citrate concentration 1 mM (Sodium Citrate MW 463.37). (pg. 6, 5th par.), which is < 0.046 wt. %.
Claims 1, 3 and 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Sato et al. (JP 2014114272 A), in view of Tokudome et al. (Tokudome et al. A new strategy for the passive skin delivery of nanoparticulate, high molecular weight hyaluronic acid prepared by a polyion complex method. Scientific Reports: 8:2336, 2018) and further in view of Liu et al. (US 2012/0295869 A1) and Berbely et al. (US 2008/0160096 A1).
Sato et al.’s and Tokudome et al.’s teachings are described in claims 1-3 and 5-6 above.
Sato et al. teach the citrate concentration in the citrate buffer is preferably 0.1 to 10 mM. (pg. 4, 11th and 12th par.). The ionic strength based on the citrate salt only (as in claim 1 of the instant application), as pH in between 6.5-7, the citrate buffer, which has pKa1 3.13, pKa2 4.76 and pKa 3 6.4, is ionized to 3H+ and citrate-3. The ionic strength:
I = 1/2 * Σ(Ci * Zi^2)
For 0.1x10-3 concentration: ½(0.1x3x12 + 0.1x32) = 0.6 x 10-3
For 10x10-3 concentration: ½(10x3x12 + 10x32) = 60 x 10-3 = 0.06 > 0.01 and 0.06 < 1.
Sato et al. and Tokudome et al. teach the method to prepare HA particles without adding a salt into water or a buffer.
Liu et al. teach solution comprising hyaluronic acid and one or more buffer components. The aqueous solution also has anionic strength equivalent to an aqueous concentration of sodium chloride. (0011). The increase in ionic strength of the aqueous hyaluronic acid solutions as a 'salt shrink wrapping, random coiled HA (0021).
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Berbely et al. teach the self-assembling nature of the nano particle provides a simple means of (i) particle preparation without resorting to chemical cross-linking, organic solvents (0010). Once the nanoparticles were formed at specific pH and salt concentration, the nanosystem is stable (0018). Nanoparticles formed from Chitosan (CHIT) and Hyaluronic Acid (HYAL). CHIT and HYAL were dissolved in water. HCl and NaOH were added later resulting in stable nanoSystems. (Example 3, 0029).
Claims 1 and 8-9
Liu et al. teach hyaluronic acid (HA) was prepared by adding a dry blended mixture of HA and NaC1 to purified water. (0035). Coiled hyaluronic acid (HA) was prepared by slowly adding a dry blended mixture of HA and NaC1 to purified water. The HA appeared fully dissolved after about 20 min. (0035). Since NaCl was dissolved in water instantly, while HA took 20 minutes to dissolve, so this method is similarly to adding HA to NaCl solution to prepare HA nanoparticles.
Berbely et al. teach the self-assembling nature of the nano particle provides a simple means of (i) particle preparation without resorting to chemical cross-linking, organic solvents (0010). Once the nanoparticles were formed at specific pH and salt concentration, the nanosystem is stable (0018). Nanoparticles formed from Chitosan (CHIT) and Hyaluronic Acid (HYAL). CHIT and HYAL were dissolved in water. HCl was added. After one-hour NaOH was added, forming NaCl resulting in stable nanoSystems. (Example 3, 0029). In this case, hyaluronic acid is blended into water and the salt is added by adding NaOH. And in the case of nanoparticles formed from CHIT ad HA, the concentration of CHIT was varied in the range 0.1 mg/ml-1.0 mg/ml, and of HYAL 0.04 0.2 mg/ml. The pH value of solutions was adjusted to pH 3 with 0.10 mol/dm3 hydrochloric acid. The ratio of polyelectrolyte and the order of mixing were modulated. After 1 hour mixing the pH was increased with 0.1 M sodium hydroxide Solution resulting in stable nanoSystems. (0029), where the ionic strength is 0.1 mol/dm3 or 0.1 mol/L. (0029). Even with a different percentage of HA, still the ionic strength of the salt is within the range of 0.01-1.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare cosmetic compositions, comprising a citrate buffer solution (aqueous), with ionic strength in between 0.1 and 1, taught by Sato et al., and to have HA nanoparticle less than 200 nm, with 90% HA, taught by Tokudome et al., and to use the salt to prepare HA taught by Liu et al. and Berbely et al. and to have salt NaCl in water while HA dissolved and formed particles, taught by Liu et al., or to have NaCl in water later to prepare HA nanoparticles since they have proven it is suitable to do so.
Claims 1, 3 and 10,
Liu et al. teach an appropriate amount of the dry hyaluronic acid is added to a dry blending vessel along with an appropriate amount of sodium chloride. The two powders are dry blended effectively diluting the hyaluronic acid in the sodium chloride. (0039).
Berbely et al. teach the self-assembling nature of the chitosan and hyaluronic acid nanoparticle preparation with HCl and NaOH, which form NaCl salt in the mixture to prepare HA nanoparticles. (Example 3, 0029).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare cosmetic compositions, comprising a citrate buffer solution (aqueous), with ionic strength in between 0.1 and 1, taught by Sato et al., and to have HA nanoparticle less than 200 nm, with 90% HA, taught by Tokudome et al., and to use salt to prepare coiled HA taught by Liu et al. and chitosan and hyaluronic acid nanoparticle, taught by Berbely et al. since they have proven it is suitable to do so.
Response to Arguments
35 U.S.C. § 103 Rejection Claims
Applicant argues that Sato does not teach hyaluronic acid at a ratio of more than 90% by mass or more, based on the total polymer amount contained in the hyaluronic acid particle, and the content ratio of the other polymer component other than the hyaluronic acid in the hyaluronic acid particle is 10% by mass or less, based on the total polymer amount contained in the hyaluronic acid particle. The Office Action cited Berkland to cure this deficiency. However, Berkland describes that "the crosslinked HA ( or CS) polymer chains become less soluble (hydrophilic) and were suggested to transform from coils to globules" (paragraph [0109]). Thus, it is clear that the invention described in Berkland obtains hyaluronic acid particles by using crosslinking method. Accordingly, the combination of Sato and Berkland would not arrive at the present claims.
Applicant's arguments have been fully considered and they are persuasive according to previous office action, however, they are not persuasive according to this office action because of the amendment the hyaluronic acid particle is not crosslinked, so prior art Berkland is removed and new prior art Tokudome is substituted. Tokudome teaches delivery of hyaluronic acid into the skin. Hyaluronic acid nanoparticles are prepared by mixing negatively charged HA with positively charged protamine (PRT). HA-PRT NPs are prepared at different ratios of HA:PRT by mixed them at different rations 10:90-90:10, to have NPs from 101.8-151.5 nm diameter. And with that particle size, HA can be higher than 90% and particle size could be less than 200 nm.
Applicant argues that claim 8 and 9 are amended to add the ionic strength of 0.01-1.0 of molar concentration of salt, Sato, Berkland, Liu, and Berbely would not arrive at the present claims.
Applicant's arguments have been fully considered but they are not persuasive because Sato still teaches ionic strength of citric sodium salt. And Berbely also teaches in the case of nanoparticles formed from CHIT ad HA. The pH value of solutions was adjusted to pH 3 with 0.10 mol/dm3 hydrochloric acid. The ratio of polyelectrolyte and the order of mixing were modulated with 0.1 M sodium hydroxide solution, (0029), where the ionic strength is 0.1 mol/dm3 or 0.1 mol/L, even with lower percentage of HA, but one with skill in the art can learn of ionic strength from both Sato and Berbely.
Conclusion
Applicants' amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Correspondence
No claim is allowed
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/NGOC-ANH THI NGUYEN/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615