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 .
Claims 1-16 are pending examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 1/8/2024 and 4/1/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
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 1-16 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.
Claim 1 recites the first agent in a liquid formulation “comprising an aqueous solution containing chitosan and phosphate ion” and also claims “an aqueous solution containing chitosan” and “an aqueous solution containing phosphate ions” which is confusing. It is unclear if the first agent comprises chitosan and phosphate ions” or if the first agent only comprises “chitosan”. It appears the aqueous solutions must be separate to meet the limitation of the claim. It appears that the phosphate ions constitutes an agent different from the first agent. Therefore, the metes and bounds of the term first agent cannot be deciphered and has been treated as an agent comprising chitosan and phosphate ions.
Claims 1 and 12 recite “phosphate ions” and the full scope of what is encompassed by this term cannot be deciphered. It is unclear if the source of the phosphate ions are limited to the inorganic phosphates such as those of claim 3, any phosphate source or also include phosphate ions from organic compounds. The metes and bounds of the term cannot be deciphered. For the purpose of examination the term has been treated as any inorganic or organic compound comprising phosphate.
Claim 8 recites “further comprises a third agent comprising a basic aqueous solution for changing strength of the hydrogel composition” which is indefinite. The metes and bounds of what is encompassed by the term is unclear. The specification describes the “a basic aqueous solution” may include ammonia, alkali hydroxides and alkali carbonates, however the full scope of the term is vague and unclear. For the purpose of examination the limitation has been treated as encompassing any ingredient which changes alter properties of the final hydrogel composition, including buffers, thickeners, plasticizers and other auxiliary agents. Claim 8 recites the limitation "the hydrogel composition" and there is insufficient antecedent basis for this limitation in the claim.
Claims 2-16 are rejected for depending on rejected base claims 1 and 12.
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, 6, 8, 9, 11, 12, 14 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Dyer et al. (US2008/0248991; published October 9, 2008).
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, and the weight ratio chitosan to phosphate ions is 1:0.01 parts by weight to 1:03 parts by weight. (claim 1)
With respect to claims 1, 6, 9, 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 9 and 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.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art to combine the teachings of Dyer et al. to 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, 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. 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.
Claim(s) 3, 5, 7, 13 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Dyer et al. (US2008/0248991; published October 9, 2008) as applied to claims 1, 2, 4, 6, 8, 9, 11, 12, 14 and 16 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, and the weight ratio chitosan to phosphate ions is 1:0.01 parts by weight to 1:03 parts by weight. (claim 1)
The teachings of Dyer et al. are addressed in the above response.
With respect to claim 3, 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.
Claim(s) 10 is rejected under 35 U.S.C. 103 as being unpatentable over Dyer et al. (US2008/0248991; published October 9, 2008) as applied to claims 1, 2, 4, 6, 8, 9, 11, 12, 14 and 16 in 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, and the weight ratio chitosan to phosphate ions is 1:0.01 parts by weight to 1:03 parts by weight. (claim 1)
The teachings of Dyer et al. are addressed in the above response.
Dyer et al. does not specify 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].
Both Dyer 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. 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. 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.
Claim(s) 1, 2, 4, 6, 8, 9 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Cha et al. (KR102100506; published April 13, 2020).
Applicant claims 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, and the weight ratio chitosan to phosphate ions is 1:0.01 parts by weight to 1:03 parts by weight. (claim 1)
Cha et al. disclose a chitosan hydrogel composition comprising chitosan, glycerol and a phosphoric acid group, wherein temperature control can induce the composition in a liquid state into a gel state according to the ratio of the phosphoric acid group and the glycerol (abstract). The chitosan may be cross-linked by glycerol, phosphate groups, or combinations thereof [0015; paragraph 1]. The chitosan hydrogel can control the strength of the composition by controlling the type and content of the crosslinking agent, specifically wherein the glycerol an phosphate groups are in a ratio of 1:10 to 10:1 [0015; paragraph 8-10]. A gelatin solution was first prepared and afterwards 0.6 g of chitosan was added and the 0.3 ml of a mixed solution of 0.25-0.5M disodium phosphate and 0.5 M glycerol was added and after storage the solution became a gel [0025-33; Examples 1-5].
With respect to claims 1, 4 and 12, Cha et al. do not teach the weight ratio of chitosan to phosphate ions is 1:0.1 to 1:0.3, preferably 1:0.16 to 1:0.18. and 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 Cha et al. teach the glycerol an phosphate groups are in a ratio of 1:10 to 10:1 to achieve gelation.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art to combine the teachings of Cha et al. to adjust the weight ratio of chitosan to phosphate ions to 1:0.1 to 1:0.3, preferably 1:0.16 to 1:0.18 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 Cha et al. because one of ordinary skill would have been able to achieve the ratios by routine optimization.
Conclusion
No claims allowed.
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DANIELLE D. JOHNSON
Examiner
Art Unit 1617
/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611