Polynucleotides encoding anti-chikungunya virus antibodies
AssigneesModernaTX, Inc., Vanderbilt University
InventorsSunny Himansu, James E. Crowe, Jr., Giuseppe Ciaramella
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Abstract
This disclosure relates to compositions and methods for treating and preventing chikungunya virus infection by delivering polynucleotides encoding anti-chikungunya virus antibodies to a subject. Compositions and treatments provided herein include one or more polynucleotides having an open reading frame encoding an anti-chikungunya virus antibody heavy chain or fragment thereof and/or an anti-chikungunya virus antibody light chain or fragment thereof. Methods for preparing and using such treatments are also provided.
Claims85
A polynucleotide comprising an mRNA comprising:
- (i) a 5′ UTR;
- (ii) an open reading frame (ORF) encoding a polypeptide comprising the heavy chain variable region of the heavy chain antibody sequence of SEQ ID NO:1, wherein the ORF comprises a nucleic acid sequence that is at least 80% identical to nucleotides 61-426 of SEQ ID NO:2;
- (iii) a stop codon;
- and
- (iv) a 3′ UTR.
A polynucleotide comprising an mRNA comprising:
- (i) a 5′ UTR;
- (ii) an open reading frame (ORF) encoding a polypeptide comprising the light chain variable region of the light chain antibody sequence of SEQ ID NO:3, wherein the ORF comprises a nucleic acid sequence that is at least 80% identical to nucleotides 61-384 of SEQ ID NO:4;
- (iii) a stop codon;
- and
- (iv) a 3′ UTR.
A pharmaceutical composition comprising:
- a first polynucleotide comprising a first mRNA comprising (i) a first 5′ UTR, (ii) a first open reading frame (ORF) encoding a first polypeptide comprising the heavy chain variable region of the heavy chain antibody sequence of SEQ ID NO:1, wherein the first ORF comprises a first nucleic acid sequence that is at least 80% identical to nucleotides 61-426 of SEQ ID NO:2, (iii) a first stop codon, and (iv) a first 3′ UTR;
- a second polynucleotide comprising a second mRNA comprising (i) a second 5′ UTR, (ii) a second ORF encoding a second polypeptide comprising the light chain variable region of the light chain antibody sequence of SEQ ID NO:3, wherein the second ORF comprises a second nucleic acid sequence that is at least 80% identical to nucleotides 61-384 of SEQ ID NO:4, (iii) a second stop codon, and (iv) a second 3′ UTR;
- and
- a delivery agent,
- wherein the first polypeptide when paired with the second polypeptide forms an anti-Chikungunya virus antibody or an anti-Chikungunya virus antibody fragment.
A pharmaceutical composition comprising a first mRNA comprising a first open reading frame (ORF) encoding a first polypeptide comprising a heavy chain variable region of an anti-chikungunya virus antibody and a second mRNA comprising a second ORF encoding a second polypeptide comprising a light chain variable region of the anti-chikungunya virus antibody, wherein the first polypeptide and the second polypeptide pair to form the anti-chikungunya virus antibody, and wherein the pharmaceutical composition when administered to a human subject in need thereof as a single dose administration is sufficient to:
- (i) protect the human subject from chikungunya virus infection, after exposure to a chikungunya virus, for at least 24 hours, 48 hours, 72 hours, 96 hours, 168 hours, 336 hours, or 720 hours after the single dose administration;
- (ii) protect the human subject from onset of chikungunya fever, after exposure to a chikungunya virus, for at least 24 hours, 48 hours, 72 hours, 96 hours, 168 hours, 336 hours, or 720 hours after the single dose administration;
- and/or
- (iii) provide systemic production of the anti-chikungunya virus antibody in the human subject at a level of at least 5 μg/ml, 10 μg/ml, 15 μg/ml, 20 μg/ml, 25 μg/ml, or 30 μg/ml for at least 24 hours, 48 hours, 72 hours, 96 hours, 168 hours, 336 hours, or 720 hours after the single dose administration.
Dependencies are inferred from the claim text.