US2024016890A1PendingUtilityA1

Methods and compositions for preventing or treating cancer

71
Assignee: UNIV UTAH RES FOUNDPriority: Oct 8, 2015Filed: Oct 3, 2023Published: Jan 18, 2024
Est. expiryOct 8, 2035(~9.2 yrs left)· nominal 20-yr term from priority
Inventors:Joshua SchiffmanAvi SchroederLisa Abegglen
A61K 38/1758A61K 31/7105A61K 31/711A61K 9/127A61K 45/06C07K 14/47A61K 9/51C07K 14/4746A61K 48/00A61P 35/00A61K 9/5146
71
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Claims

Abstract

The present disclosure is directed to methods and compositions for inhibiting a cancer cell using nucleic acid sequences encoding elephant p53 or elephant p53 amino acid sequences.

Claims

exact text as granted — not AI-modified
1 . A method of inhibiting cancer, which comprises contacting a cancer cell with (a) one or more nucleic acid sequences each encoding an elephant p53 protein, or (b) one or more elephant p53 proteins, whereby the cancer is inhibited. 
     
     
         2 . The method of  claim 1 , which comprises contacting the cancer cell with one or more nucleic acid sequences each encoding an elephant p53 protein. 
     
     
         3 . The method of  claim 2 , wherein a nucleic acid sequence encoding an elephant p53 protein is a retrogene. 
     
     
         4 . The method of  claim 2 , wherein a nucleic acid sequence encoding an elephant p53 protein is an ancestral gene. 
     
     
         5 . The method of  claim 2 , which comprises contacting the cancer cell with multiple nucleic acid sequences, each encoding an elephant p53 protein. 
     
     
         6 . The method of  claim 5 , wherein the multiple nucleic acid sequences comprise multiple different retrogenes. 
     
     
         7 . The method of  claim 6 , wherein at least one of the multiple nucleic acid sequences comprises an ancestral gene. 
     
     
         8 . The method of any of  claims 1 - 7 , wherein the one or more nucleic acid sequences comprise RNA or DNA. 
     
     
         9 . The method of  claim 3  or  claim 6 , wherein the retrogene comprises a nucleic acid sequence of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 14, SEQ ID NO: 16, SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 22, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 32, SEQ ID NO: 34, SEQ ID NO: 36, SEQ ID NO: 38, SEQ ID NO: 40, SEQ ID NO: 42, SEQ ID NO: 44, SEQ ID NO: 46, SEQ ID NO: 48, SEQ ID NO: 50, SEQ ID NO: 52, SEQ ID NO: 54, SEQ ID NO: 56, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 62, SEQ ID NO: 64, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQ ID NO: 72, SEQ ID NO: 74, or SEQ ID NO: 76. 
     
     
         10 . The method of  claim 4  or  claim 7 , wherein the ancestral gene comprises a nucleic acid sequence of SEQ ID NO: 2. 
     
     
         11 . The method of  claim 1 , which comprises contacting the cancer cells with one or more elephant p53 proteins. 
     
     
         12 . The method of  claim 11 , which comprises contacting the cancer cell with one elephant p53 protein. 
     
     
         13 . The method of  claim 12 , wherein the elephant p53 protein is encoded by a retrogene. 
     
     
         14 . The method of  claim 13 , wherein the elephant p53 protein is encoded by an ancestral gene. 
     
     
         15 . The method of  claim 11 , which comprises contacting the cancer cell with multiple different elephant p53 proteins. 
     
     
         16 . The method of  claim 15 , wherein the multiple different elephant p53 proteins are encoded by multiple different retrogenes. 
     
     
         17 . The method of  claim 16 , wherein at least one of the multiple different elephant p53 proteins is an ancestral p53 protein. 
     
     
         18 . The method of  claim 13  or  claim 16 , wherein the P53 protein comprises an amino acid sequence of SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 29, SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 35, SEQ ID NO: 37, SEQ ID NO: 39, SEQ ID NO: 41, SEQ ID NO: 43, SEQ ID NO: 45, SEQ ID NO: 47, SEQ ID NO: 49, SEQ ID NO: 51, SEQ ID NO: 53, SEQ ID NO: 55, SEQ ID NO: 57, SEQ ID NO: 59, SEQ ID NO: 61, SEQ ID NO: 63, SEQ ID NO: 65, SEQ ID NO: 67, SEQ ID NO: 69, SEQ ID NO: 71, SEQ ID NO: 73, SEQ ID NO: 75, and SEQ ID NO: 77. 
     
     
         19 . The method of  claim 14  or  claim 17 , wherein the p53 protein comprises an amino acid sequence of SEQ ID NO: 3. 
     
     
         20 . The method of any one of  claims 1 - 19 , wherein the one or more nucleic acid sequences or the one or more elephant p53 proteins are in the form of a composition, which composition comprises a pharmaceutically-acceptable carrier. 
     
     
         21 . The method of  claim 20 , wherein the composition comprises a liposome. 
     
     
         22 . The method of  claim 21 , wherein the one or more nucleic acid sequences or one or more p53 proteins are encapsulated within the liposome. 
     
     
         23 . The method of  claim 20 , wherein the composition comprises a nanoparticle. 
     
     
         24 . The method of  claim 23 , wherein the nanoparticle comprises one or more fillers selected from the group consisting of an organic substance, an inorganic substance, a lipid, a polymer, a metal, and a carbon nanostructure. 
     
     
         25 . The method of  claim 23  or  24 , wherein the nanoparticle comprises the elephant p53 protein or elephant TP53 nucleic acid encapsulated within a liposome. 
     
     
         26 . The method of any one of  claims 23 - 25 , wherein the nanoparticle comprises an external surface decorated with a moiety for reducing an interaction with the reticuloendothelial system. 
     
     
         27 . The method of  claim 26 , wherein the moiety comprises polyethylene glycol. 
     
     
         28 . The method of  claim 26 , wherein the moiety comprises a targeting moiety. 
     
     
         29 . The method of  claim 28 , wherein the targeting moiety increases the affinity of the nanoparticle for the cancer cell. 
     
     
         30 . The method of any one of  claims 20 - 29 , wherein the composition further comprises one or more additives selected from the group consisting of a small molecule chemotherapeutic, a monoclonal antibody, and an imaging agent. 
     
     
         31 . The method of  claim 30 , wherein the imaging agent comprises a contrast agent, a sugar, an iron complex, or gadolinium (Gd). 
     
     
         32 . The method of any one of  claims 1 - 31 , wherein the cancer cell is in vitro or in vivo. 
     
     
         33 . The method of any one of  claims 1 - 32 , wherein the cancer cell is derived from a mammal. 
     
     
         34 . The method of  claim 33 , wherein the mammal is a human. 
     
     
         35 . A composition comprising a pharmaceutically acceptable carrier and (a) one or more nucleic acid sequences each encoding an elephant p53 protein or (b) one or more elephant p53 proteins. 
     
     
         36 . The composition of  claim 34 , which comprises one or more nucleic acid sequences each encoding an elephant p53 protein. 
     
     
         37 . The composition of  claim 34  or  35 , wherein the one or more nucleic acid sequences comprise RNA or DNA. 
     
     
         38 . The composition of  claim 34 , which comprises one or more elephant p53 proteins. 
     
     
         39 . The composition of  claim 34 , which comprises a liposome. 
     
     
         40 . The composition of  claim 38 , wherein the one or more nucleic acid sequences or one or more P53 proteins are encapsulated within the liposome. 
     
     
         41 . The composition of  claim 34 , which comprises a nanoparticle. 
     
     
         42 . The composition of  claim 40 , wherein the nanoparticle comprises one or more fillers selected from the group consisting of an organic substance, an inorganic substance, a lipid, a polymer, a metal, and a carbon nanostructure. 
     
     
         43 . The composition of  claim 40  or  claim 41 , wherein the one or more nucleic acid sequences or one or more p53 proteins are encapsulated within a liposome. 
     
     
         44 . The composition of any one of  claims 40 - 42 , wherein the nanoparticle comprises an external surface decorated with a moiety for reducing an interaction with the reticuloendothelial system. 
     
     
         45 . The composition of  claim 43 , wherein the moiety comprises polyethylene glycol. 
     
     
         46 . The composition of  claim 43 , wherein the moiety comprises a targeting moiety. 
     
     
         47 . The composition of  claim 45 , wherein the targeting moiety increases the affinity of the nanoparticle for the cancer cell. 
     
     
         48 . The composition of any one of  claims 34 - 46 , which further comprises one or more additives selected from the group consisting of a small molecule chemotherapeutic, a monoclonal antibody, and an imaging agent. 
     
     
         49 . The composition of  claim 47 , wherein the imaging agent comprises a contrast agent, a sugar, an iron complex, or gadolinium (Gd).

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