Chitosan-derived compositions
Inventors
Hode, Tomas • Nordquist, Robert • Chen, Wei R. • Carubelli, Raoul • Alleruzzo, Luciano • Jenkins, Peter • Waynant, Kristopher • Raker, Joseph
Assignees
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Publication Number
US-11111316-B2
Publication Date
2021-09-07
Expiration Date
Abstract
The present invention relates generally to therapeutic compositions comprising chitosan-derived compositions used in connection with methods for treating neoplasms, such as for instance, malignant lung, thyroid and kidney neoplasms, and other types of malignant neoplasms, and other medical disorders.
Core Innovation
The disclosed invention relates to chitosan-derived compositions and, in particular, viscoelastic glycated chitosan polymers defined by molecular weight, degree of deacetylation, degree of glycation, and DP. The invention provides a glycated chitosan within specified ranges, including molecular weight about 100,000 to about 300,000 Daltons, a degree of deacetylation about 75% to about 99%, and a degree of glycation of free amino groups about 0.1% to about 30%. The compositions are formulated as sterile aqueous solutions formulated for injection.
The invention addresses limitations of conventional glycated chitosan regarding injectability and sterile filtration by linking rheology and viscosity to the polymer’s molecular weight, degree of deacetylation, degree of glycation, and DP. The formulations are described as enabling easier needle injection and improved sterile filtration, thereby supporting cGMP manufacturing and sterile filtration performance. Reported formulation parameters include an injectable solution pH of about 5–7 and viscosity in the range of about 1–100 cP at 25° C.
The invention further connects these injectable glycated chitosan compositions to neoplasm treatment through in situ immunotherapy concepts, including in situ autologous cancer vaccine (inCVAX) and laser-assisted immunotherapy (LIT), and also to photodynamic therapy (PDT) contexts. The disclosed examples include a breast cancer human trial with RECIST-based outcomes and preclinical animal studies in which laser-assisted immunotherapy with glycated chitosan formulations is described as improving survival and tumor-specific immunity.
Claims Coverage
The document provided contains three independent claims. Across these claims, the core inventive content is the use of a glycated chitosan with defined molecular weight, degree of deacetylation, and degree of glycation, in a sterile injectable aqueous formulation, and its intratumoral use for generating an in situ autologous vaccine and for enhancing an immune system response to an antigen. The remaining provided claim text indicates additional formulation constraints such as sterile filtration and an aqueous pH range, but the main inventive content is captured by the three independent claims’ quantitative and intratumoral delivery limitations.
Sterile injectable aqueous glycated chitosan formulation with defined molecular weight, deacetylation, and glycation
A pharmaceutical formulation comprising a glycated chitosan having a molecular weight of about 100,000 to about 300,000 Daltons, wherein the glycated chitosan has a degree of deacetylation of about 75% to about 99% and a degree of glycation of free amino groups of about 0.1% to about 30%, and further wherein the pharmaceutical formulation is a sterile aqueous solution formulated for injection.
In situ autologous vaccine generation by intratumoral introduction of a glycated chitosan formulation after neoplasm ablation
A method of generating an in situ autologous vaccine, comprising ablating a neoplasm in a host, thereby releasing fragmented neoplastic tissue and cellular molecules; and introducing a pharmaceutical formulation comprising a glycated chitosan into the neoplasm, wherein the glycated chitosan has a molecular weight of about 100,000 to about 300,000 Daltons, a degree of deacetylation of about 75% to about 99%, and a degree of glycation of free amino groups of about 0.1% to about 30%.
Enhancing immune system response by intratumoral administration of a glycated chitosan formulation
A method of enhancing immune system response to an antigen in a patient in need thereof, comprising administering a pharmaceutical formulation comprising a glycated chitosan into the neoplasm, wherein the glycated chitosan has a molecular weight of about 100,000 to about 300,000 Daltons, a degree of deacetylation of about 75% to about 99%, and a degree of glycation of free amino groups of about 0.1% to about 30%.
Overall, the independent claims are centered on defined-characteristic glycated chitosan materials and their use in a sterile aqueous injectable formulation administered into a neoplasm. The claims further frame therapeutic utility as generating an in situ autologous vaccine following neoplasm ablation and as enhancing immune system response to an antigen.
Stated Advantages
Enables easier needle injection.
Improves sterile filtration, including suitability for cGMP manufacturing.
Reduces patient pain.
Documented Applications
Generating an in situ autologous vaccine by ablating a neoplasm and introducing a glycated chitosan pharmaceutical formulation into the neoplasm.
Enhancing immune system response to an antigen by administering a glycated chitosan pharmaceutical formulation into the neoplasm.
Laser-assisted immunotherapy (LIT) for neoplasm treatment using glycated chitosan formulations, with reported improved survival and tumor-specific immunity in described mouse/rat studies.
Photodynamic therapy (PDT) contexts discussed in connection with glycated chitosan formulations.
Human breast cancer trial with RECIST-based responses (including CR/PR/SD and objective response rate) associated with the described treatment context.
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