Compositions and methods for delivering therapeutic polynucleotides
OwnerElias Quijano, Peter Glazer +2inventors
InventorsElias Quijano, Peter Glazer, Bruce C. Turner, Stephen Squinto
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Abstract
Compositions and methods are provided for delivering therapeutic polynucleotides by administering a complex formed between a therapeutic polynucleotide having a 3E10 or 3E10 variant binding domain and a 3E10 antibody or variant thereof, or antigen-binding fragment thereof. In some instances, the complexes are stabilized through a molar ratio of 3E10 antibody or variant thereof, or antigen-binding fragment thereof to therapeutic polynucleotide of at least about 2:1.
Claims27
A pharmaceutical composition comprising a therapeutically effective amount of a complex formed between (i) a 3E10 antibody or variant thereof, or antigen-binding fragment thereof;
- and (ii) a therapeutic polynucleotide comprising a 3E10 or 3E10 variant binding domain that is preferably bound by the 3E10 or 3E10 variant antibody.
3-14. (canceled)
The pharmaceutical composition of claim 10, wherein the 3E10 or 3E10 variant binding domain comprises a first mononucleotide repeat sequence of at least 10 nucleotides in length.
The pharmaceutical composition of claim 6, wherein:
- the VH CDR 1 has the amino acid sequence of 3E10-VH-CDR1_D3IN (SEQ ID NO:15);
- the therapeutic polynucleotide is single-stranded DNA;
- and
- the 3E10 or 3E10 variant binding domain has a dT content of greater than 25%.
The pharmaceutical composition of claim 6, wherein:
- the VH CDR 1 has the amino acid sequence of 3E10-VH-CDR1_D3IN (SEQ ID NO:15);
- the therapeutic polynucleotide is single-stranded DNA;
- and
- the 3E10 or 3E10 variant binding domain has a dA content of less than 25%.
The pharmaceutical composition of claim 6, wherein:
- the VH CDR1 has the amino acid sequence of 3E10-VH-CDR1_D3IN (SEQ ID NO:15);
- the therapeutic polynucleotide is single-stranded RNA;
- and
- the 3E10 or 3E10 variant binding domain has a rI content of greater than 25%.
The pharmaceutical composition of claim 6, wherein:
- the VH CDR 1 has the amino acid sequence of 3E10-VH-CDR1_D3IN (SEQ ID NO:15);
- the therapeutic polynucleotide is single-stranded RNA;
- and
- the 3E10 or 3E10 variant binding domain has a rG content of greater than 25%.
The pharmaceutical composition of claim 6, wherein:
- the VH CDR 1 has the amino acid sequence of 3E10-VH-CDR1_D3IN (SEQ ID NO:15);
- the therapeutic polynucleotide is single-stranded RNA;
- and
- the 3E10 or 3E10 variant binding domain has a combined rl and rG content of greater than 25%.
-28. (canceled)
-32. (canceled)
(canceled)
37-105. (canceled)
A pharmaceutical composition comprising a therapeutically effective amount of a composition comprising a complex formed between (i) a 3E10 antibody or variant thereof, or antigen-binding fragment thereof, and (ii), a therapeutic polynucleotide wherein:
- the therapeutic polynucleotide comprises a first codon-altered nucleotide sequence encoding a therapeutic polypeptide;
- and
- the 3E10 antibody or variant thereof, or antigen-binding fragment thereof has a greater affinity for the first codon-altered nucleotide sequence than for a second nucleotide sequence that encodes the therapeutic polypeptide using a same coding sequence for the therapeutic polypeptide as found in a genome for the species of the subject.
107-180. (canceled)
A method for delivering a therapeutic polynucleotide to a tissue of a subject in vivo, the method comprising parenterally administering a pharmaceutical composition comprising a therapeutically effective amount of a complex formed between (i) a 3E10 antibody or variant thereof, or antigen-binding fragment thereof;
- and (ii) a therapeutic polynucleotide comprising a 3E10 or 3E10 variant binding domain that is preferably bound by the 3E10 or 3E10 variant antibody to the subject.
182-198. (canceled)
Dependencies are inferred from the claim text.