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 .
Applicant’s amendment filed 7/2/2026 has been entered. Claim 3 was canceled. Claims 1, 9 and 12 were amended. Claims 1, 2 and 4-16 are pending examination.
Withdrawn rejections
Applicant's amendments and arguments filed 7/2/2026 are acknowledged and have been fully considered. Any rejection and/or objection not specifically addressed below is herein withdrawn.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 1, 2, 4-8 and 11-16 are rejected under 35 U.S.C. 103 as being unpatentable over Dyer et al. (US2008/0248991; published October 9, 2008) in view of Gerges et al. (WO 2022/074427; published April 14, 2022).
Applicant claims a compositions comprising a first agent in a liquid formulation comprising and aqueous solution containing 0.05-3.5 wt% chitosan and 0.1-40 wt% phosphate ions selected from sodium phosphate dibasic and potassium phosphate monobasic, and the weight ratio chitosan to phosphate ions is 1:0.1 parts by weight to 1:0.3 parts by weight. (claim 1)
With respect to claims 1, 6, 11, 12, 14 and 16, Dyer et al. teach a composition comprising chitosan, a polyol-phosphate or sugar-phosphate salt, a plasticizer and a therapeutic agent which is typically a solution or suspension at ambient temperature but forms a gel a physiological temperatures (abstract). The chitosan is in the form of an aqueous solution or suspension and is preferably in an amount ranging from 0.25-3% w/v [0016]. The polyol-phosphate or sugar-phosphate is also in the form of an aqueous solution or suspension and preferably range from 0.25-3% w/v [0021]. The polyol-phosphate and sugar phosphate are mono-phosphate dibasic salts that are preferably derivatives of glycerol [0019 limitation of claim 6 and 14]. The plasticizer interacts with the chitosan to alter the physical and mechanical properties and reduces the temperature at which gelation occurs and include citrates, preferably 0.05-5% w/v [0022-23; limitation of claim 16]. Dyer et al. teach that chitosan glutamate with a deacetylation of 83% requires 3.4 moles of phosphate ion from glycerol-phosphate to neutralize each mole of chitosan while chitosan base having a degree of deacetylation of 92.6% requires 1.6 moles of phosphate ion [0060]. Example 1 details preparing 18.8 mg/mL chitosan glutamate solution in water and adding 150 mg/mL glycerophosphate solution chilled on ice with stirring with onset of gelation being 0-5 minutes [0075-77].
Claim 2 is drawn to inherent properties of the formulation.
With respect to claims 1, 4 and 12, Dyer et al. do not teach the weight ratio of chitosan to phosphate ions is 1:0.01 to 1:0.3, preferably 1:0.16 to 1:0.18, however, the Dyer et al. teach chitosan and phosphate ranges from 0.25-3% so a ratio of 3:0.25 (1:0.08) overlaps with the ratio. With respect to claim 8, Dyer et al. do not specify the second agent comprises 0.10-14 parts by weight of the glycerol per 1 part of chitosan solution. However, one of ordinary skill would have been able to achieve the ratios by routine optimization because Dyer et al. teach chitosan with higher deacetylation requires less moles of phosphate ions to achieve gelation. Since the phosphate ion separate from the glycerol in solution it would naturally follow that the phosphate ions and glycerol portion would be in equal amounts in the formulation. One of ordinary skill in the art would have been motivated before the time of filing to combine the teachings of Dyer et al. further adjust the weight ratio of chitosan to phosphate ions is 1:0.1 to 1:0.3 preferably 1:0.16 to 1:0.18 because Dyer et al. teach ranges that overlap and one of ordinary skill would have been able to achieve the ratios with routine optimization.
With respect to claim 1, Dyer et al. does not teach phosphate ions are from sodium phosphate dibasic and potassium phosphate monobasic. With respect to claims 5 and 7 Dyer et al. do not teach the agents further comprise decellularized matrix. With respect to claim 13, Dyer et al. is silent to the step of stabilizing the first agent for 1 hour to 7 days. With respect to claim 15, Dyer et al. is silent to the mixture including the first and second agent under in vivo conditions. It is for this reason that Gerges et al. is joined.
Gerges et al. teach implantable biodegradable polymeric matrix which have high biocompatibility [0011-12]. The matrix include decellularized matrices [0016]. The matrix is easily injectable into an organism by means of a needle of tube [0033]. After implantation the phase transition from solid to liquid state results in change due to temperature [0038]. The preferred embodiment has a matrix which releases to deliver to local tissue near the implantation site in vivo [0040]. The matrix reduces the foreign body response when [0042]. The decellularized matrix is seeded in vitro with cells and living tissue [0050]. Example 7 details curable chitosan having a deacetylation degree in the range of 30-90% where two solutions were prepared one comprising chitosan and phosphate buffer solution (PBS 1X) and stabilized for 5-35 hours prior to being mixed with a second dipeptide cysteinyl-cysteine and laminin peptide mixtures in phosphate buffer saline [0072-73].
As evidenced by Chazotte (Labeling Golgi with Flourescent Ceramides, 2012) PBS 1X solution is prepared by mixing 8g sodium chloride, 0.2g potassium chloride, 1.44g sodium phosphate dibasic and 0.24 potassium phosphate monobasic (page 915)
Both Dyer et al. and Gerges et al. are drawn to chitosan formulations in phosphate solutions which form temperature sensitive hydrogels. Therefore, it would have been prima facie obvious to one of ordinary skill in the art to combine the teachings of Dyer et al. and Gerges et al. to include a mixture of sodium phosphate dibasic and potassium phosphate monobasic and stabilizing the first agent for 1 hour to 7 days with a reasonable expectation of success. One of ordinary skill in the art would have been motivated before the time of filing to combine the teachings of Dyer et al. and Gerges et al. further include sodium phosphate dibasic and potassium phosphate monobasic because Gerges et al. teach chitosan is stabilized 5-35 hours with 1X PBS buffer which comprises sodium phosphate dibasic and potassium phosphate monobasic.
It would have been prima facie obvious to one of ordinary skill in the art to combine the teachings of Dyer et al. and Gerges et al. to include a decellularized matrix and to include the first and second agent under in vivo conditions with a reasonable expectation of success. One of ordinary skill in the art would have been motivated before the time of filing to combine the teachings of Dyer et al. and Gerges et al. because Gerges et al. teach decellularized matrix which releases to deliver to local tissue near the implantation site in vivo which is more biocompatible.
Response to Arguments
Applicant's arguments filed 7/2/2026 have been fully considered but they are not persuasive.
Applicant argues the specific weight ratio of the solution demonstrates soft tissue restoration for facial areas and periorbital fillers. The Examiner has considered these arguments, however any differences between the claimed invention and the prior art may be expected to result in some differences in properties. Dyer et al. teach that plasticizers interacts with the chitosan to alter the physical and mechanical properties [0022-23]. Dyer et al. teach ranges that overlap and one of ordinary skill would have been able to achieve the ratios with routine optimization. Additionally, Gerges et al. teach implantable biodegradable polymeric matrix which have high biocompatibility [0011-12]. Applicant has failed to show that the claimed ratios demonstrate unexpected results commensurate in scope with the claimed invention. To establish unexpected results applicants should compare a sufficient number of tests to demonstrate the criticality of the claimed range In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960).
Claim(s) 9 is rejected under 35 U.S.C. 103 as being unpatentable over Dyer et al. (US2008/0248991; published October 9, 2008) in view of Gerges et al. (WO 2022/074427; published April 14, 2022) as applied to claims 1, 2, 4-8 and 11-16 in further view of Sparkes et al. (US 4,572,906; patented February 25, 1986).
Applicant claims a compositions comprising a first agent in a liquid formulation comprising and aqueous solution containing 0.05-3.5 wt% chitosan and 0.1-40 wt% phosphate ions selected from sodium phosphate dibasic and potassium phosphate monobasic, and the weight ratio chitosan to phosphate ions is 1:0.1 parts by weight to 1:0.3 parts by weight. (claim 1)
The teachings of Dyer et al. and Gerges et al. are addressed in the above response.
Dyer et al. and Gerges et al. do not specify that a third agent comprising a basic aqueous solution comprising ammonia, sodium carbonate or sodium hydroxide. It is for this reason that Sparkes et al. is joined.
Sparkes et al. teach wound dressings comprising a blend of gelatin and chitosan which form hydrogels (abstract; column 6, lines 54-61). The wound dressing material is prepared by dissolving chitosan in water with pH of about 2-5, adding gelatin dissolved in water and mixing (column 3, lines 30-54). After mixing the acidic chitosan solution with gelatin the pH is often less than 5 however it is desirable to raise the pH to minimize pain and tissue damage with a 5% sodium hydroxide, aqueous sodium bicarbonate or aqueous ammonia without affecting flexibility of the gel (column 4, lines 3-32).
Dyer et al., Gerges et al. and Sparks et al. are drawn hydrogels formulations. Therefore, it would have been prima facie obvious to one of ordinary skill in the art to combine the teachings of Dyer et al., Gerges et al. and Sparks et al. to include a basic solution comprising sodium hydroxide, aqueous sodium bicarbonate or aqueous ammonia with a reasonable expectation of success. One of ordinary skill in the art would have been motivated before the time of filing to combine the teachings of Dyer et al., Gerges et al. and Sparks et al. further include sodium hydroxide, aqueous sodium bicarbonate or aqueous ammonia because Sparks et al. it is desirable to raise pH of the chitosan solution with these ingredients to minimize pain and tissue damage.
Claim(s) 10 is rejected under 35 U.S.C. 103 as being unpatentable over Dyer et al. (US2008/0248991; published October 9, 2008) in view of Gerges et al. (WO 2022/074427; published April 14, 2022) as applied to claims 1, 2, 4-8 and 11-16 in further view of Kim et al. (US 2021/0290825; published September 23, 2021).
Applicant claims a compositions comprising a first agent in a liquid formulation comprising and aqueous solution containing 0.05-3.5 wt% chitosan and 0.1-40 wt% phosphate ions selected from sodium phosphate dibasic and potassium phosphate monobasic, and the weight ratio chitosan to phosphate ions is 1:0.1 parts by weight to 1:0.3 parts by weight. (claim 1)
The teachings of Dyer et al. and Gerges et al. are addressed in the above response.
Dyer et al. and Gerges et al. do not specify that the first agent and the second agent are isolated in separate spaces within a container. It is for this reason that Kim et al. is joined.
Kim et al. teach injection formulations comprising a first biopolymer and a second liquid comprising a second biopolymer (abstract). The injectable hydrogels are prepared by the first liquid and the second liquid in a state separated from each other in a dual syringe and when mixed they crosslink through click chemistry reaction [0030].
Dyer et al., Gerges et al. and Kim et al. are drawn hydrogels formulations. Therefore, it would have been prima facie obvious to one of ordinary skill in the art to combine the teachings of Dyer et al., Gerges et al. and Kim et al. to include the first agent and the second agent isolated in separate spaces within a container with a reasonable expectation of success. One of ordinary skill in the art would have been motivated before the time of filing to combine the teachings of Dyer et al., Gerges et al. and Kim et al. further include the first agent and the second agent isolated in separate spaces within a dual syringe because Kim et al. teach injectable hydrogels prepared by the first liquid and the second liquid in a state being separated from each other in a dual syringe so that they do not mix and only initiate crosslinking after injection in the body.
Conclusion
No claims allowed.
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 nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANIELLE D JOHNSON whose telephone number is (571)270-3285. The examiner can normally be reached Monday-Friday 9:00 am-5:30 pm.
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/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611
DANIELLE D. JOHNSON
Examiner
Art Unit 1617
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