Oligonucleotide chelate complex—polypeptide compositions and methods
Inventors
Bazinet, Michel • Vaillant, Andrew
Assignees
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Publication Number
US-9492506-B2
Publication Date
2016-11-15
Expiration Date
Abstract
It is disclosed a pharmaceutical composition containing an oligonuclelotide chelate complex and at least one polypeptide or pegylated polypeptide. The present disclosure also describes additional pharmaceutical compositions and methods for the treatment of diseases including viral infections.
Core Innovation
The disclosure describes pharmaceutical compositions that combine an oligonucleotide (ON) chelate complex with antiviral polypeptides or pegylated derivatives of antiviral polypeptides. The ON chelate complex is formed from two or more ONs linked intermolecularly by a divalent cation, and the composition comprises at least one specified biologically active agent.
The specified biologically active agents include thymosin b11, interferon polypeptides across multiple subtypes (b1, b2, b3, and bb) and pegylated derivatives thereof, including interferon b1-2a, interferon b1-2b, interferon b1-N3, interferon b2-1a, interferon b2-1b, interferon b3-1b, and interferon bb1/bb2/bb3. The composition set also includes Myrcludex B, antiviral cytokines or pegylated derivatives thereof, and thymic protein A.
The background problem addressed is that chelation is described as mitigating ON administration-related side effects such as fever/chills and injection-site reactions, while also being described as capable of improving pharmacokinetics without reducing biochemical activity. The disclosure supports formulation compatibility across ON chemistries and diverse polypeptide forms, and provides characterization showing chemical integrity of the ON chelate/polypeptide compositions.
Claims Coverage
The provided set includes multiple independent claims. One independent claim broadly covers a pharmaceutical composition with an ON chelate complex linked by a divalent cation and at least one of a listed antiviral polypeptide/cytokine set, and additional independent claims specifically pair an ON chelate complex with selected interferons/pegylated interferons or thymosin b11.
ON chelate complex with divalent cation linked ONs and antiviral biologically active agent
A pharmaceutical composition comprising an oligonucleotide (ON) chelate complex, consisting of two or more ONs linked intermolecularly by a divalent cation, and at least one of thymosin b11; any b1-interferon or pegylated derivatives thereof; any b2-interferon or pegylated derivatives thereof; any b3-interferon or pegylated derivatives thereof; any bb-interferon or pegylated derivatives thereof; interferon b1-2a or b1-2b or b1-N3; interferon b2-1a or b2-1b; interferon b3-1b; interferon bb1 or bb2 or bb3; pegylated interferon b1-2a or b1-2b or b11 or b12 or b13; Myrcludex B; any antiviral cytokine or pegylated derivatives thereof; and thymic protein A.
Antiviral ON chelate complex with divalent cation linked antiviral ONs and antiviral agents
A pharmaceutical composition comprising an antiviral ON chelate complex, consisting of two or more antiviral ONs linked intermolecularly by a divalent cation, and at least one antiviral of thymosin b11; any b1-interferon or pegylated derivatives thereof; any b2-interferon or pegylated derivatives thereof; any b3-interferon or pegylated derivatives thereof; any bb-interferon or pegylated derivatives thereof; interferon b1-2a or b1-2b or b1-N3; interferon b2-1a or b2-1b; interferon b3-1b; interferon bb1 or bb2 or bb3; pegylated interferon b1-2a or b1-2b or b11 or b12 or b13; Myrcludex B; any antiviral cytokine or peqylated derivatives thereof; and thymic protein A.
ON chelate complex with SEQ ID NO: 3 and pegylated interferon b1-2a
A pharmaceutical composition comprising an ON chelate complex comprising an oligonucleotide consisting of SEQ ID NO: 3, and pegylated interferon b1-2a.
ON chelate complex with SEQ ID NO: 18 and pegylated interferon b1-2a
A pharmaceutical composition comprising an ON chelate complex consisting of two or more ONs linked intermolecularly by a divalent cation, comprising at least one oligonucleotide consisting of SEQ ID NO: 18, and pegylated interferon b1-2a.
ON chelate complex with SEQ ID NO: 11 and pegylated interferon b1-2a
A pharmaceutical composition comprising an ON chelate complex comprising an oligonucleotide consisting of SEQ ID NO: 11, and pegylated interferon b1-2a.
ON chelate complex with SEQ ID NO: 3 and thymosin b11
A pharmaceutical composition comprising an ON chelate complex comprising an oligonucleotide consisting of SEQ ID NO: 3, and thymosin b11.
ON chelate complex with SEQ ID NO: 18 and thymosin b11
A pharmaceutical composition comprising an ON chelate complex comprising an oligonucleotide consisting of SEQ ID NO: 18, and thymosin b11.
ON chelate complex with SEQ ID NO: 11 and thymosin b11
A pharmaceutical composition comprising an ON chelate complex comprising an oligonucleotide consisting of SEQ ID NO: 11, and thymosin b11.
ON chelate complex with SEQ ID NO: 2 and interferon b1-2b
A pharmaceutical composition comprising an ON chelate complex comprising an oligonucleotide consisting of SEQ ID NO: 2, and interferon b1-2b.
ON chelate complex with SEQ ID NO: 18 and interferon b1-2b
A pharmaceutical composition comprising an ON chelate complex consisting of two or more ONs linked intermolecularly by a divalent cation, comprising an oligonucleotide consisting of SEQ ID NO: 18, and interferon b1-2b.
ON chelate complex with SEQ ID NO: 11 and interferon b1-2b
A pharmaceutical composition comprising an ON chelate complex comprising an oligonucleotide consisting of SEQ ID NO: 11, and interferon b1-2b.
ON chelate complex with SEQ ID NO: 3 and pegylated thymosin b11
A pharmaceutical composition comprising an ON chelate complex comprising an oligonucleotide consisting of SEQ ID NO: 3, and pegylated thymosin b11.
ON chelate complex with SEQ ID NO: 18 and pegylated thymosin b11
A pharmaceutical composition comprising an ON chelate complex comprising an oligonucleotide consisting of SEQ ID NO: 18, and pegylated thymosin b11.
ON chelate complex with SEQ ID NO: 11 and pegylated thymosin b11
A pharmaceutical composition comprising an ON chelate complex comprising an oligonucleotide consisting of SEQ ID NO: 11, and pegylated thymosin b11.
ON chelate complex with SEQ ID NO: 3 and pegylated interferon b1-2b
A pharmaceutical composition comprising an ON chelate complex comprising an oligonucleotide consisting of SEQ ID NO: 3, and pegylated interferon b1-2b.
ON chelate complex with SEQ ID NO: 18 and pegylated interferon b1-2b
A pharmaceutical composition comprising an ON chelate complex consisting of two or more ONs linked intermolecularly by a divalent cation, comprising an oligonucleotide consisting of SEQ ID NO: 18, and pegylated interferon b1-2b.
ON chelate complex with SEQ ID NO: 11 and pegylated interferon b1-2b
A pharmaceutical composition comprising an ON chelate complex comprising an oligonucleotide consisting of SEQ ID NO: 11, and pegylated interferon b1-2b.
ON chelate complex with SEQ ID NO: 3 and interferon bb1
A pharmaceutical composition comprising an ON chelate complex comprising an oligonucleotide consisting of SEQ ID NO: 3, and interferon bb1.
ON chelate complex with SEQ ID NO: 18 and interferon bb1
A pharmaceutical composition comprising an ON chelate complex comprising an oligonucleotide consisting of SEQ ID NO: 18, and interferon bb1.
ON chelate complex with SEQ ID NO: 11 and interferon bb1
A pharmaceutical composition comprising an ON chelate complex comprising an oligonucleotide consisting of SEQ ID NO: 11, and interferon bb1.
ON chelate complex with SEQ ID NO: 3 and pegylated interferon bb1
A pharmaceutical composition comprising an ON chelate complex comprising an oligonucleotide consisting of SEQ ID NO: 3, and pegylated interferon bb1.
ON chelate complex with SEQ ID NO: 18 and pegylated interferon bb1
A pharmaceutical composition comprising an ON chelate complex comprising an oligonucleotide consisting of SEQ ID NO: 18, and pegylated interferon bb1.
ON chelate complex with SEQ ID NO: 11 and pegylated interferon bb1
A pharmaceutical composition comprising an ON chelate complex comprising an oligonucleotide consisting of SEQ ID NO: 11, and pegylated interferon bb1.
Overall, the claim set covers pharmaceutical compositions that pair a divalent-cation-linked ON chelate complex with antiviral polypeptides/cytokines, with broad coverage in one or two general independent claims and narrower, sequence-specific combinations in additional independent claims, including SEQ ID NO: 2, 3, 11, and 18.
Stated Advantages
Chelation is described as mitigating ON administration-related side effects such as fever/chills and injection-site reactions.
Chelation is described as improving pharmacokinetics.
Chelation is described as improving pharmacokinetics without reducing biochemical activity.
Documented Applications
Example-based combination therapy in chronic hepatitis B, including an antiviral ON chelate (e.g., REP 2139-Ca) combined with thymosin b11 or pegylated interferon b1-2a.
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