Compositions comprising neoantigens and methods of enhancing anti-pd1 therapy
AssigneesThe Wistar Institute of Anatomy and Biology, Geneos Therapetucis, Inc.
InventorsPratik S. Bhojnagarwala, Niranjan Y. Sardesai, David B. Weiner
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Abstract
The disclosure relates to methods of treating cancer in a subject administering nucleic acid molecules comprising a nucleic acid sequence encoding a plurality of neoantigens. Vaccines, compositions comprising coding regions encoding neoantigens organized in a pattern of nucleic acid sequences are also disclosed as well as methods of immunizing a subject using the same.
Claims33
1-14. (canceled)
A pharmaceutical composition comprising:
- (i) one or a plurality of nucleic acid molecules, or a pharmaceutically acceptable salt thereof;
- (ii) one or more checkpoint inhibitors or a nucleic acid sequence that encodes one or more checkpoint inhibitors;
- and (iii) a pharmaceutically acceptable carrier;
- wherein the one or plurality of nucleic acid molecules comprise an expressible nucleic acid sequence encoding a polypeptide comprising a concatemer of a linked series of neoantigens or antigenic determinants thereof, and comprises Formula I:
- (AED1)-(linker)1-(AED2)-(linker)2-(AED3)-
- (linker)3- . . . (AEDn)-(linker)n-
- AEDn+1,
- each AED encodes one of the neoantigens or antigenic determinants thereof,
- each linker has a length independently selectable from about 15 to about 300 natural or non-natural nucleotides,
- wherein the length of each AED is independently selectable from about 90 to about 250 nucleotides;
- and
- wherein n is any positive integer from about 19 to about 100.
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-33. (canceled)
-47. (canceled)
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-56. (canceled)
A method of enhancing the efficacy of a PD-1 inhibitor in a subject in need thereof comprising administering to the subject a therapeutically effective amount of one or a plurality of nucleic acid molecules, or a pharmaceutically acceptable salt thereof;
- wherein the one or plurality of nucleic acid molecules comprise an expressible nucleic acid sequence encoding a polypeptide comprising a concatemer of a linked series of neoantigens or antigenic determinants thereof, and comprises Formula I:
- (AED1)-(linker)1-(AED2)-(linker)2-(AED3)-
- (linker)3- . . . (AEDn)-(linker)n-
- AEDn+1,
- each AED encodes one of the neoantigens or antigenic determinants thereof, each linker has a length independently selectable from about 15 to about 300 natural or non-natural nucleotides, and wherein the length of each AED is independently selectable from about 90 to about 250 nucleotides;
- and wherein n is any positive integer from about 19 to about 100.
-64. (canceled)
Dependencies are inferred from the claim text.