Loading...
Please wait, while we are loading the content...
Similar Documents
T Cell Binding Proteins
| Content Provider | The Lens |
|---|---|
| Description | La divulgation concerne de manière générale des protéines de liaison qui comprennent des sites de liaison à l'antigène, un site de liaison de récepteur de lymphocytes T et un site de liaison de molécule de co-stimulation de lymphocytes T. La divulgation concerne également des compositions comprenant de telles protéines de liaison et des molécules d'acide nucléique codant de telles protéines de liaison. La divulgation concerne en outre des méthodes de traitement d'un trouble ou d'un état pathologique utilisant de telles protéines de liaison. |
| Abstract | The disclosure generally relates to binding proteins that comprise antigen binding sites, a T cell receptor binding site, and a T cell co-stimulatory molecule binding site. The disclosure also provides compositions comprising such binding proteins and nucleic acid molecules encoding such binding proteins. The disclosure further relates to methods of treating a disorder or condition using such binding proteins. |
| Related Links | https://www.lens.org/images/patent/WO/2023198635/A1/WO_2023_198635_A1.pdf |
| Language | English |
| Publisher Date | 2023-10-19 |
| Access Restriction | Open |
| Alternative Title | Protéines De Liaison À Des Lymphocytes T |
| Content Type | Text |
| Resource Type | Patent |
| Date Applied | 2023-04-06 |
| Agent | Astrazeneca Intellectual Property |
| Applicant | Astrazeneca Ab |
| Application No. | 2023059278 |
| Claim | A binding protein comprising four polypeptide chains that form two tumor-associated antigen binding sites, a T cell receptor binding site, and a T cell co-stimulatory molecule binding site, wherein the first and second polypeptide chains have a structure represented by the formula: VL-CL and a third polypeptide chain has a structure represented by the formula: VHI-CHI-VH2-FC and a fourth polypeptide chain has a structure represented by the formula: VHI-CHI-VH3-FC wherein: VL is an immunoglobulin light chain variable domain that specifically binds a tumor- associated antigen; VHI is an immunoglobulin heavy chain variable domain that specifically binds a tumor- associated antigen; CL is an immunoglobulin light chain constant domain that specifically binds a tumor- associated antigen; CHI is an immunoglobulin CHI heavy chain constant domain that specifically binds a tumor-associated antigen; VH2 is a heavy chain variable domain that specifically binds a T cell receptor; VH3 is a heavy chain variable domain that specifically binds T cell co-stimulatory molecule; and Fc is CH2 and CH3 immunoglobulin heavy chain constant domains. The binding protein of claim 1 further comprising Li, a linker positioned between CHI and VH2 on the third polypeptide chain and L2, a linker positioned between VH2 and the Fc on the third polypeptide chain, wherein Li and L2 are each independently a linker or are absent. The binding protein of claim 1 or claim 2 further comprising L3, a linker positioned between CHI and VH3 on the fourth polypeptide chain and L4, a linker positioned between VH3 and Fc on the fourth polypeptide chain wherein L3 and L4 are each independently a linker or are absent. The binding protein of any one of claims 1-3 further comprising Hi, an immunoglobulin hinge region positioned between CHI and VH2 on the third polypeptide chain and H2, an immunoglobulin hinge region positioned between VH2 and the Fc on the third polypeptide chain, wherein Hi and H2 are each independently an immunoglobulin hinge region or are absent. The binding protein of any one of claims 1-4 further comprising H3, an immunoglobulin hinge region positioned between CHI and VH3 on the fourth polypeptide chain and H4, an immunoglobulin hinge region positioned between VH3 and the Fc on the fourth polypeptide chain, wherein H3 and H4 are each independently an immunoglobulin hinge region or are absent. The binding protein of any one of claims 1-5, wherein the first and second polypeptide chains have a structure represented by the formula: VL-CL and a third polypeptide chain has a structure represented by the formula: VHI-CHI-HI-LI-VH2-H2-L2-FC and a fourth polypeptide chain has a structure represented by the formula: VHI-CHI- H3-L3-VH3- H4-L4-FC. The binding protein of any one of claims 1-6, wherein the Fc is from an IgG antibody. The binding protein of any one of claims 1-7, wherein the binding protein activates T cells only when bound to a tumor associated antigen at one or both of the antigen binding sites. The binding protein of any one of claims 1-8, wherein the tumor-associated antigen is CD20. The binding protein of any one of claims 1-9, wherein the T cell costimulatory molecule is CD8 or CD137. A binding protein comprising four polypeptide chains that form two tumor-associated antigen binding sites, a T cell receptor binding site, and a T cell co-stimulatory molecule binding site, wherein two polypeptide chains have a structure represented by the formula: VL-CL and two polypeptide chains have a structure represented by the formula: III-VHI-CHI-VH2-FC-II2; wherein: Fc is CH2 and CH3 immunoglobulin heavy chain constant domains; III and II2 are each independently a heavy chain variable domain that specifically binds a T cell co-stimulatory molecule or are absent; wherein at least one of II 1 and II2 is a heavy chain variable domain that specifically binds a T cell co-stimulatory molecule. III-VL-CL-IF; and two polypeptide chains have a structure represented by the formula: VHI-CHI-VH2-FC; wherein: -se VL is an immunoglobulin light chain variable domain that specifically binds a tumor- associated antigen; A binding protein comprising three polypeptide chains that form two tumor-associated antigen binding sites, a T cell receptor binding site, and a T cell co-stimulatory molecule binding site, wherein the first polypeptide chain has a structure represented by the formula: VL-CL and a second polypeptide chain has a structure represented by the formula: VHI-CHI-VH2-FC and a third polypeptide chain has a structure represented by the formula: VHI-VH3-FC wherein: CL is an immunoglobulin light chain constant domain that specifically binds a tumor- associated antigen; CHI is an immunoglobulin CHI heavy chain constant domain that specifically binds a tumor-associated antigen; The binding protein of any one of claims 11-13, wherein the binding protein activates T cells only when bound to a tumor associated antigen at one or both of the antigen binding sites. The binding protein of any one of claims 11-14, wherein the tumor-associated antigen is CD20. The binding protein of any one of claims 11-15, wherein the T cell costimulatory molecule is CD8 or CD137. A binding protein comprising four polypeptide chains that form two tumor-associated antigen binding sites, a T cell receptor binding site, and a T cell co-stimulatory molecule binding site, wherein the polypeptide chains comprise (a) the amino acid of sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3; (b) the amino acid of sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 4; (c) the amino acid of sequences of SEQ ID NO: 1, SEQ ID NO: 9, and SEQ ID NO: 10; (d) the amino acid of sequences of SEQ ID NO: 1, SEQ ID NO: 11, and SEQ ID NO: 12; (e) the amino acid of sequences of SEQ ID NO: 1, SEQ ID NO: 13, and SEQ ID NO: 14; (f) the amino acid of sequences of SEQ ID NO: 1 and SEQ ID NO: 19; (g) the amino acid of sequences of SEQ ID NO: 1, SEQ ID NO: 22, and SEQ ID NO: 23; (h) the amino acid of sequences of SEQ ID NO: 29 and SEQ ID NO: 30; (i) the amino acid of sequences of SEQ ID NO: 31 and SEQ ID NO: 32; (j) the amino acid of sequences of SEQ ID NO: 33 and SEQ ID NO: 34; (k) the amino acid of sequences of SEQ ID NO: 35 and SEQ ID NO: 36; (l) the amino acid of sequences of SEQ ID NO: 37 and SEQ ID NO: 38; (m) the amino acid of sequences of SEQ ID NO: 39 and SEQ ID NO: 40; (n) the amino acid of sequences of SEQ ID NO: 41 and SEQ ID NO: 42; or (o) the amino acid of sequences of SEQ ID NO: 45, and SEQ ID NO: 54. A binding protein comprising three polypeptide chains that form two tumor-associated antigen binding sites, a T cell receptor binding site, and a T cell co-stimulatory molecule binding site, wherein the polypeptide chains comprise the amino acid of sequences of SEQ ID NO: 43, SEQ ID NO: 44, and SEQ ID NO: 45 or (q) the amino acid of sequences of SEQ ID NO: 1, SEQ ID NO: 11 and SEQ ID NO: 12. A pharmaceutical composition comprising the binding protein of any one of claims 1-18 and a pharmaceutically acceptable carrier. An isolated nucleic acid sequence encoding the binding protein of claim 17 or claim 18. A vector comprising the isolated nucleic acid sequence of claim 20. A method of treating cancer, comprising administering to a subject in need thereof an effective amount of the binding protein of any one of claims 1-18. The method of claim 22, wherein the binding protein preferentially activates a subset of T cells in the subject. The method of either claim 22 or 23, wherein the subset of T cells are CD8 T cells. The method of any one of claims 22-24, wherein the CD8 T cells are preferentially activated as compared to CD4 T cells. The method of claim 23, wherein the activation of T cells is determined by measuring the percentage of surface CD25+ T cells. The method of claim 26, wherein the percentage of surface CD25+ T cells that are CD8 T cells is higher than the percentage of surface CD25+ T cells that are CD4 T cells. A method of treating an inflammatory disease, comprising administering to a subject in need thereof an effective amount of the binding protein of any one of claims 1-18. A binding protein according to any one of claims 1-18, or a pharmaceutical composition according to claim 19, for use as a medicament. A binding protein according to any one of claims 1-18, or a pharmaceutical composition according to claim 19, for use in the treatment of cancer. A binding protein according to any one of claims 1-18, or a pharmaceutical composition according to claim 19, for use in the treatment of an inflammatory disease. Use of a binding protein according to any one of claims 1-18, or a pharmaceutical composition according to claim 19, in the manufacture of a medicament for use in the treatment of cancer. Use of a binding protein according to any one of claims 1-18, or a pharmaceutical composition according to claim 19, in the manufacture of a medicament for use in the treatment of an inflammatory disease. |
| CPC Classification | PEPTIDES Specific Therapeutic Activity Of Chemical Compounds Or Medicinal Preparations Preparations For Medical; Dental Or Toiletry Purposes |
| Extended Family | 088-261-576-350-803 |
| Patent ID | 2023198635 |
| Inventor/Author | Cobbold Mark Cayatte Corinne Seaman Jonathan Christopher Joel |
| IPC | C07K16/28 A61P35/02 |
| Status | Pending |
| Simple Family | 088-261-576-350-803 |
| CPC (with Group) | C07K2317/55 C07K2317/569 C07K2317/64 C07K2317/52 C07K2317/51 C07K2317/515 C07K2317/35 C07K2317/31 C07K2319/50 C07K2317/73 C07K2317/75 C07K16/2809 A61P35/02 A61K2039/505 C07K16/2887 C07K16/2878 C07K16/2815 |
| Issuing Authority | World Intellectual Property Organization (WIPO) |
| Kind | Patent Application Publication |
