公开(公告)号：US12220456B2

公开(公告)日：2025-02-11

申请号：US18436426

申请日：2024-02-08

Applicant: Combined Therapeutics, Inc.

Inventor： Romain Micol ,  Valerie Duval

IPC: A61K39/215 ,  C12N15/11 ,  C12N15/113 ,  A61K39/00

Abstract: Compositions are provided comprising messenger RNA constructs having at least one open reading frame (ORF), wherein the ORF is operatively linked to at least one untranslated region (UTR), wherein the UTR comprises at least one organ protection sequence (OPS), wherein the OPS sequence comprises at least a first, a second and a third micro-RNA (miRNA) target sequence, and wherein each of the at least a first, second and third the miRNA target sequences are optimised to hybridise with a corresponding miRNA sequence. The compositions and molecules provided are useful in therapies such as for the treatment of cancer, in immunotherapies, and in vaccines.

公开(公告)号：US20220220506A1

公开(公告)日：2022-07-14

申请号：US17706522

申请日：2022-03-28

Applicant: Combined Therapeutics, Inc.

Inventor： Romain Micol

IPC: C12N15/86 ,  A61K31/7088 ,  A61K35/763 ,  A61K45/06 ,  A61K48/00

Abstract: A composition for expressing a polypeptide within a target organ, the composition comprising a delivery particle, and at least a first mRNA sequence complexed with, encapsulated by, or otherwise associated with the delivery particle. The mRNA sequence comprises a coding sequence which codes for the polypeptide, at least a first untranslated region (UTR) sequence, and at least one micro-RNA (miRNA) binding site sequence, wherein the miRNA binding site sequence is located within, immediately 5′ to, or immediately 3′ to, the first UTR sequence. The miRNA binding site sequence is selected so as to provide for differential expression of the coding sequence between first and second cell types comprised within the target organ. The composition may be used in combination with or to supplement other therapeutic approaches, including chemotherapy, oncolytic viral therapy, and cellular therapies. Methods for making and using the composition are provided, particularly in treatment of disease, such as cancer of the liver, brain, lung, breast and pancreas.

公开(公告)号：US20200376142A1

公开(公告)日：2020-12-03

申请号：US16970888

申请日：2019-02-19

Applicant: Combined Therapeutics, Inc.

Inventor： Romain Micol

IPC: A61K48/00 ,  A61K45/06 ,  A61K35/763

Abstract: An isolated mRNA sequence for expression of one or more polypeptides within one or more target organs, the sequence comprising at least one coding sequence which codes for the at least one polypeptide, at least a first untranslated region (UTR) sequence and a plurality of micro-RNA (miRNA) binding site sequences. Each oft he miRNA binding site sequences is located within, immediately 5′ to or immediately 3′ to, the first UTR sequence; and the miRNA binding site sequences allow for differential expression of the coding sequence in at least a first and a second cell type within the target organ or organs Methods for using the composition are provided, particularly in treatment of disease, such as cancer of the liver, brain, lung, breast, pancreas, colon and kidney.

公开(公告)号：US20230241206A1

公开(公告)日：2023-08-03

申请号：US18108248

申请日：2023-02-10

Applicant: Combined Therapeutics, Inc.

Inventor： Romain Micol ,  Valerie Duval

IPC: A61K39/215 ,  C12N15/113

CPC classification number: A61K39/215 ,  C12N15/113 ,  A61K2039/53

Abstract: Compositions are provided comprising messenger RNA constructs having at least one open reading frame (ORF), wherein the ORF is operatively linked to at least one untranslated region (UTR), wherein the UTR comprises at least one organ protection sequence (OPS), wherein the OPS sequence comprises at least a first, a second and a third micro-RNA (miRNA) target sequence, and wherein each of the at least a first, second and third the miRNA target sequences are optimised to hybridise with a corresponding miRNA sequence. The compositions and molecules provided are useful in therapies such as for the treatment of cancer, in immunotherapies, and in vaccines.

公开(公告)号：US11359212B2

公开(公告)日：2022-06-14

申请号：US16811504

申请日：2020-03-06

Applicant: Combined Therapeutics, Inc.

Inventor： Romain Micol ,  Slawomir Antoszczyk

IPC: C12N15/86 ,  A61K31/7088 ,  A61K35/763 ,  A61K45/06 ,  A61K48/00

Abstract: Compositions for expressing a polypeptide within a target organ, the composition comprising a delivery particle, and at least a first mRNA sequence complexed with, encapsulated by, or otherwise associated with the delivery particle, wherein the mRNA sequence comprises at least one coding sequence which codes for at least one polypeptide, at least a first untranslated region (UTR) sequence, and at least one micro-RNA (miRNA) binding site sequence, wherein the miRNA binding site sequence is located within, immediately 5′ to, or immediately 3′ to, the first UTR sequence; and wherein the miRNA binding site sequence provides for differential expression of the coding sequence between first and second cell types comprised within the target organ.

公开(公告)号：US20240024451A1

公开(公告)日：2024-01-25

申请号：US18018759

申请日：2021-07-30

Applicant: Combined Therapeutics, Inc.

Inventor： Romain Micol ,  Valerie Duval

IPC: A61K39/12 ,  C07K14/54 ,  C12N15/113 ,  A61K39/04 ,  A61K39/00 ,  A61P31/14 ,  A61K48/00

CPC classification number: A61K39/12 ,  C07K14/5434 ,  C12N15/113 ,  A61K39/04 ,  A61K39/0011 ,  A61P31/14 ,  A61K48/005 ,  A61K2039/53

Abstract: Provided is a composition comprising a first mRNA construct comprising a first open reading frame (ORF), wherein the first ORF encodes an antigen; wherein the first ORF is operatively linked to at least one untranslated region (UTR), wherein the UTR comprises at least a first organ protection sequence (OPS), and wherein the first OPS comprises at least two micro-RNA (miRNA) target sequences, wherein each of the at least two miRNA target sequences are optimised to hybridise with a corresponding miRNA sequence. Also provided are further compositions comprising mRNA constructs comprising an ORF and an OPS wherein the ORF encodes a proinflammatory cytokine, and methods including one or both of these compositions for the treatment and prevention of disease such as pathogenic disease.

公开(公告)号：US20240252618A1

公开(公告)日：2024-08-01

申请号：US18436426

申请日：2024-02-08

Applicant: Combined Therapeutics, Inc.

Inventor： Romain Micol ,  Valerie Duval

IPC: A61K39/215 ,  A61K39/00 ,  C12N15/113

CPC classification number: A61K39/215 ,  C12N15/113 ,  A61K2039/53

Abstract: Compositions are provided comprising messenger RNA constructs having at least one open reading frame (ORF), wherein the ORF is operatively linked to at least one untranslated region (UTR), wherein the UTR comprises at least one organ protection sequence (OPS), wherein the OPS sequence comprises at least a first, a second and a third micro-RNA (miRNA) target sequence, and wherein each of the at least a first, second and third the miRNA target sequences are optimised to hybridise with a corresponding miRNA sequence. The compositions and molecules provided are useful in therapies such as for the treatment of cancer, in immunotherapies, and in vaccines.

公开(公告)号：US20220202932A1

公开(公告)日：2022-06-30

申请号：US17689908

申请日：2022-03-08

Applicant: Combined Therapeutics, Inc.

Inventor： Romain Micol ,  Valerie Duval

IPC: A61K39/215 ,  C12N15/113

Abstract: Compositions are provided comprising messenger RNA constructs having at least one open reading frame (ORF), wherein the ORF is operatively linked to at least one untranslated region (UTR), wherein the UTR comprises at least one organ protection sequence (OPS), wherein the OPS sequence comprises at least a first, a second and a third micro-RNA (miRNA) target sequence, and wherein each of the at least a first, second and third the miRNA target sequences are optimised to hybridise with a corresponding miRNA sequence. The compositions and molecules provided are useful in therapies such as for the treatment of cancer, in immunotherapies, and in vaccines.

公开(公告)号：US12195746B2

公开(公告)日：2025-01-14

申请号：US17706522

申请日：2022-03-28

Applicant: Combined Therapeutics, Inc.

Inventor： Romain Micol

IPC: C12N15/86 ,  A61K31/7088 ,  A61K35/763 ,  A61K45/06 ,  A61K48/00

Abstract: A composition for expressing a polypeptide within a target organ including a delivery particle, and at least a first mRNA sequence complexed with, encapsulated by, or otherwise associated with the delivery particle. The mRNA sequence includes a coding sequence which codes for the polypeptide, at least a first untranslated region (UTR) sequence, and at least one micro-RNA (miRNA) binding site sequence, wherein the miRNA binding site sequence is located within, immediately 5′ to, or immediately 3′ to, the first UTR sequence. The miRNA binding site sequence is selected so as to provide for differential expression of the coding sequence between first and second cell types comprised within the target organ. Methods for making and using the composition are provided, particularly in treatment of disease, such as cancer.

公开(公告)号：US11931409B2

公开(公告)日：2024-03-19

申请号：US18108248

申请日：2023-02-10

Applicant: Combined Therapeutics, Inc.

Inventor： Romain Micol ,  Valerie Duval

IPC: A61K39/215 ,  C12N15/11 ,  C12N15/113 ,  A61K39/00

CPC classification number: A61K39/215 ,  C12N15/113 ,  A61K2039/53

Abstract: Compositions are provided comprising messenger RNA constructs having at least one open reading frame (ORF), wherein the ORF is operatively linked to at least one untranslated region (UTR), wherein the UTR comprises at least one organ protection sequence (OPS), wherein the OPS sequence comprises at least a first, a second and a third micro-RNA (miRNA) target sequence, and wherein each of the at least a first, second and third the miRNA target sequences are optimised to hybridise with a corresponding miRNA sequence. The compositions and molecules provided are useful in therapies such as for the treatment of cancer, in immunotherapies, and in vaccines.