Aligos Therapeutics, Inc.

Janssen Biopharma, Inc.

Alios Biopharma, Inc.

Jin Hong

Leonid Beigelman

Vivek Kumar Rajwanshi

Rajendra K Pandey

Sergei M Gryaznov

Markus Hossbach

Saul Martinez Montero

Laxman Eltepu

N Tilani S De Costa

David Bernard Smith

Lawrence M Blatt

Scott D Seiwert

Yi Jin

Antitsa Dimitrova Stoycheva

Lakshmipathi Pandarinathan

Bharat Baral

Described are short interfering nucleic acid (siNA) molecules comprising modified nucleotides, compositions, and methods and uses thereof.

Modified short interfering nucleic acid (siNA) molecules and uses thereof

The present disclosure relates to compounds and compositions containing 5'-phosphoramidite nucleoside monomers, and methods of making and use.

Modified nucleoside phosphoramidites

Disclosed herein are short interfering nucleic acid (siNA) molecules comprising modified nucleotides and uses thereof. The siNA molecules may be double stranded and comprise modified nucleotides selected from 2'-O-methyl nucleotides and 2′-fluoro nucleotides. Further disclosed herein are siNA molecules comprising (a) a phosphorylation blocker, conjugated moiety, or 5′-stabilized end cap; and (b) a short interfering nucleic acid (siNA).

A method of making a compound represented by Formula (I): includes a reducing step, a protecting step, and a phosphitylating step, where X is NH; Y is OCF, —O(CR)CR, —O(CR)OCR, or —O(CR)—CR═CR; Z is H; B is adenine (A), guanine (G), thymine (T), cytosine (C), uracil (U), 5-methylcytosine (5-me-C), or a protected version of A, G, T, C, U, or 5-me-C; each Ris independently Calkyl or cycloalkyl; Ris CHCHCN or Calkyl; or Rand Rtogether form an optionally substituted Ccycloalkyl; Ris H or PG; PG is a protecting group; Ris independently in each instance H or F; a is 1 or 2; and b is 1, 2, or 3.

Disclosed herein are short interfering nucleic acid (siNA) molecules comprising modified nucleotides and uses thereof. The siNA molecules may be double stranded and comprise modified nucleotides selected from 2'-O-methyl nucleotides and 2&#x2032;-fluoro nucleotides. Further disclosed herein are siNA molecules comprising (a) a phosphorylation blocker, conjugated moiety, or 5&#x2032;-stabilized end cap; and (b) a short interfering nucleic acid (siNA).

The disclosure includes antisense oligonucleotides, including gapmer antisense oligonucleotides, along with methods of making and use, e.g., against HBV.

Modified gapmer oligonucleotides and methods of use

The present disclosure relates to compounds and compositions containing 5'-phosphoramidite nucleoside monomers of formulae (I) and (II), and methods of making and use, wherein the substituents are as defined in the appended claims. 

Various embodiments provide STOPS&#x2122; polymers that are S-antigen transport inhibiting oligonucleotide polymers, processes for making them and methods of using them to treat diseases and conditions. In some embodiments the STOPS&#x2122; modified oligonucleotides include an at least partially phosphorothioated sequence of alternating A and C units having modifications as described herein. The sequence independent antiviral activity against hepatitis B of embodiments of STOPS&#x2122; modified oligonucleotides, as determined by HBsAg Secretion Assay, is greater than that of a reference compound.

S-antigen transport inhibiting oligonucleotide polymers and methods

Modified oligonucleotides comprising modifications at the 2' and/or 3&#x2032; positions(s) along with methods of making and use, e.g., against HBV are disclosed.

Modified oligonucleotides and methods of use

The present invention provides synthetic Type I interferon receptor polypeptide agonists comprising consensus or hybrid Type I interferon receptor polypeptide agonists, containing one or more native or non-native glycosylation sites. The present invention provides synthetic Type I interferon receptor polypeptide agonists comprising consensus or hybrid Type I interferon receptor polypeptide agonists, containing one or more native or non-native glycosylation sites, as well as erythropoietin and darbepoetin alfa, each of which are linked to a penetrating peptide that facilitates translocation of a substance across a biological barrier as well as pharmaceutical compositions, including oral formulations, of the same. The present invention further provides oral formulations of hyperglycosylated or protease-resistant, hyperglycosylated polypeptide variants, which polypeptide variants lack at least one protease cleavage site found in a parent polypeptide, and thus exhibit increased protease resistance compared to the parent polypeptide, which polypeptide variants further include (1) a carbohydrate moiety covalently linked to at least one non-native glycosylation site not found in the parent protein therapeutic or (2) a carbohydrate moiety covalently linked to at least one native glycosylation site found but not glycosylated in the parent protein therapeutic. The present invention further provides compositions, including oral pharmaceutical compositions, comprising the synthetic Type I interferon receptor polypeptide agonist, the hyperglycosylated polypeptide variant, or the hyperglycosylated, protease-resistant polypeptide variant. The present invention further provides containers, devices, and kits comprising the synthetic Type I interferon receptor polypeptide agonist, the hyperglycosylated polypeptide variant, or the hyperglycosylated, protease-resistant polypeptide variant. The present invention further provides therapeutic methods involving administering an effective amount of an oral pharmaceutical composition comprising a synthetic Type I interferon receptor polypeptide agonist, a hyperglycosylated polypeptide variant, or a hyperglycosylated, protease-resistant polypeptide variant to an individual in need thereof.

Growing community of inventors

Brisbane, CA, United States of America

Jin Hong