Amino acid sequences that modulate the interaction between cells of the immune system

Patent metadata

Field	Value
Publication number	US-2016289327-A1
Application number	US-201615050740-A
Country	US
Kind code	A1
Filing date	Feb 23, 2016
Priority date	Dec 15, 2006
Publication date	Oct 6, 2016
Grant date	—

Abstract

The present invention relates to amino acid sequences that block the interaction between (a target on) an antigen presenting cell (APC) and (a target on) a T-cell. More particularly, the present invention relates to amino acid sequences that are directed against (as defined herein) a target on an APC (also referred to herein as “APC target”) or a target on a T-cell (also referred to herein as “T-cell target”). The invention further relates to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences.

First claim

1 .- 441 . (canceled)

442 . A polypeptide that binds CTLA4, that essentially consists of 4 framework regions (FR1 to FR4 respectively) and 3 complementarity determining regions (CDR1 to CDR3 respectively) in which:
CDR1 is chosen from the group consisting of: a) the amino acid sequences of SEQ ID NOs: 664-767; b) amino acid sequences that have at least 80% amino acid identity with at least one of the amino acid sequences of SEQ ID NOs: 664-767; c) amino acid sequences that have 3, 2 or 1 amino acid difference with at least one of the amino acid sequences of SEQ ID NOs: 664-676; and/or CDR2 is chosen from the group consisting of: d) the amino acid sequences of SEQ ID NOs: 872-975; e) amino acid sequences that have at least 80% amino acid identity with at least one of the amino acid sequences of SEQ ID NOs: 872-975; f) amino acid sequences that have 3, 2 or 1 amino acid difference with at least one of the amino acid sequences of SEQ ID NOs: 872-975; and/or CDR3 is chosen from the group consisting of: g) the amino acid sequences of SEQ ID NOs: 1080-1183; h) amino acid sequences that have at least 80% amino acid identity with at least one of the amino acid sequences of SEQ ID NOs: 1080-1183; i) amino acid sequences that have 3, 2 or 1 amino acid difference with at least one of the amino acid sequences of SEQ ID NOs: 1080-1183.

443 . A polypeptide according to claim 442 , that can specifically bind CTLA4 with a dissociation constant (K D ) of 10 −5 to 10 −12 moles/litre or less, 10 −7 to 10 −12 moles/litre or less or 10 −8 to 10 −12 moles/litre.

444 . A polypeptide according to claim 442 , that essentially consists of a domain antibody, a single domain antibody, VHH, a humanized VHH sequence, a camelized VH or a Nanobody®.

445 . A polypeptide according to claim 442 , that essentially consists of a Nanobody® that
a) has at least 80% amino acid identity with at least one of the amino acid sequences of SEQ ID NOs: 1-22, in which for the purposes of determining the degree of amino acid identity, the amino acid residues that form the CDR sequences are disregarded;
and in which:

b) one or more of the amino acid residues at positions 11, 37, 44, 45, 47, 83, 84, 103, 104 and 108 according to the Kabat numbering are chosen from the Hallmark residues mentioned in Table A-3.

446 . A polypeptide according to claim 442 , that essentially consists of a Nanobody® that
a) has at least 80% amino acid identity with at least one of the amino acid sequences of SEQ ID NOs: 1288-1391; in which for the purposes of determining the degree of amino acid identity, the amino acid residues that form the CDR sequences are disregarded;
and in which:
b) one or more of the amino acid residues at positions 11, 37, 44, 45, 47, 83, 84, 103, 104 and 108 according to the Kabat numbering are chosen from the Hallmark residues mentioned in Table A-3.

447 . A polypeptide according to claim 442 , that essentially consists of a Nanobody® that
a) is a humanized variant of one of amino acid sequences of SEQ ID NOs: 1288-1391;
and/or
b) has at least 80% amino acid identity with at least one of the amino acid sequences of SEQ ID NOs: 288-1391 and/or at least one of the amino acid sequences of SEQ ID NOs: 1407-1418, in which for the purposes of determining the degree of amino acid identity, the amino acid residues that form the CDR sequences are disregarded;
and in which:
c) one or more of the amino acid residues at positions 11, 37, 44, 45, 47, 83, 84, 103, 104 and 108 according to the Kabat numbering are chosen from the Hallmark residues mentioned in Table A-3.

448 . A polypeptide that cross-blocks the binding to CTLA4 by at least one of the polypeptides according to claim 442 .

449 . A polypeptide that is cross-blocked from binding to CTLA4 by at least one of the polypeptides according to claim 442 .

450 . A compound or construct, that comprises or essentially consists of one or more polypeptides according to claim 442 , and optionally further comprises one or more other groups, residues or moieties or binding units, optionally linked via one or more linkers.

451 . A compound or construct according to claim 450 , in which said one or more other groups, residues or moieties or binding units are chosen from the group consisting of domain antibodies, single domain antibodies or Nanobodies®.

452 . A compound or construct according to claim 450 , which is a multivalent or multispecific construct.

453 . A compound or construct according to claim 450 , in which said one or more other groups, residues, moieties or binding units provide the compound or construct with increased serum half-life, compared to the polypeptide without the one or more other groups, residues moieties or binding units.

454 . A compound or construct according to claim 453 , in which said one or more other groups, residues, moieties or binding units that provide the compound or construct with increased serum half-life is chosen from the group consisting of serum proteins or fragments thereof, binding units that can bind to serum proteins, an Fc portion, and small proteins or peptides that can bind to serum proteins.

455 . A compound or construct according to claim 453 , in which said one or more other groups, residues, moieties or binding units that provide the compound or construct with increased serum half-life are selected from the group consisting of human serum albumin and fragments thereof.

456 . A compound or construct according to claim 453 , in which said one or more other groups, residues, moieties or binding units that provide the compound or construct with increased serum half-life are selected from the group consisting of binding units that can bind to serum albumin, human serum albumin, and a serum immunoglobulin.

457 . A compound or construct according to claim 453 , in which said one or more other groups, residues, moieties or binding units that provide the compound or construct with increased serum half-life are selected from the group consisting of domain antibodies, single domain antibodies or Nanbodies®, that can bind to serum albumin, human serum albumin, or a serum immunoglobulin.

458 . A compound or construct according to claim 453 , that has a serum half-life that is at least 1.5 times, at least 2 times, at least 5 times, at least 10 times or more than 20 times, greater than the half-life of the polypeptide without the one or more groups, residues, moieties or binding units.

459 . A nucleic acid or nucleotide sequence, that encodes a polypeptide according to claim 442 .

460 . A composition, comprising at least one polypeptide according to claim 442 .

461 . A composition according to claim 460 , which is a pharmaceutical composition, that further comprises at least one pharmaceutically acceptable carrier, diluent or excipient and/or adjuvant, and that optionally comprises one or more further pharmaceutically active polypeptides and/or compounds.

Assignees

• Ablynx Nv

Inventors

• Hermans Guy
• Verheesen Peter
• Dolk Edward
• Hoogenboom Hendricus Renerus Jacobus Mattheus
• Saunders Michael John Scott
• De Haard Hans
• De Bruin Renee

Classifications

• A61P37/02

  Immunomodulators · CPC title

• C07K2317/567

  Framework region [FR] · CPC title

• C07K2319/31

  fusions, other than Fc, for prolonged plasma life, e.g. albumin · CPC title

• C07K16/2818 Primary

  against CD28 or CD152 · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title